Publications by authors named "Madhumita Roy"

47 Publications

Draft Whole-Genome Sequence of sp. Strain PNB, a Versatile Polycyclic Aromatic Hydrocarbon-Degrading Bacterium.

Microbiol Resour Announc 2021 Dec 2;10(48):e0092021. Epub 2021 Dec 2.

Department of Microbiology, Bose Institute, Kolkata, India.

sp. strain PNB can completely degrade phenanthrene, naphthalene, and biphenyl as the sole carbon and energy source. The strain is also capable of cometabolizing benzo[a]pyrene, pyrene, acenaphthene, fluoranthene, etc. Here, we report the 5.69-Mb assembly and annotation of the genome sequence of strain PNB, obtained using Illumina sequencing.
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http://dx.doi.org/10.1128/MRA.00920-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638569PMC
December 2021

Chemopreventive Role of Black Tea Extract in Swiss Albino Mice Exposed to Inorganic Arsenic.

Asian Pac J Cancer Prev 2021 Nov 1;22(11):3647-3661. Epub 2021 Nov 1.

Department of Environmental Carcinogenesis and Toxicology Chittaranjan National Cancer Institute 37, S P Mukherjee Road, Kolkata, India.

Objective: Chronic exposure to inorganic arsenic (iAs) may cause a number of health problems including skin cancer. Present study is aimed to look into the potential of black tea extract (BTE) to prevent the development of skin carcinoma in Swiss albino mice.

Methods: The study was done on Swiss albino mice, chronically exposed to inorganic arsenic. 150 mice were housed in different cages, 5 in each cage. The control mice did not receive any treatment. Mice were sacrificed at 30, 90, 180, 270 and 330 days. Development of carcinogenesis was assessed by histological studies. Generation of Reactive Oxygen Species (ROS) and Reactive Oxygen Species (RNS) were estimated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Greiss reagent respectively, and their consequences on DNA (by Micronuclei and Comet assay), protein (by protein carbonyl assay kit) and lipid (by lipid peroxidation) were estimated. Activity of antioxidant enzymes, along with total antioxidant capacity were measured by respective kits. Repair percentage was obtained by Comet assay. Western blotting was employed to study the expression of repair enzymes and expression of cytokines. Sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique was employed to study the activity of various cytokines.

Results: At 330 days, invasive squamous cell carcinoma of the skin developed. With increasing time generation of ROS and RNS increased, causing damage to DNA, protein and lipid. Antioxidant defence system gets repressed with time. Capacity to repair the DNA damage is inhibited by iAs, due to alteration in repair enzymes - XRCC I, DNA Ligase I, PARP I, ERCC1, ERCC2, XPA, DNA Ligase IV, DNA PKc and Ku-70. Another consequence of iAs exposure is chronic inflammation due to disrupted cytokine level. Intervention with BTE reverses these deleterious effects, preventing development of skin carcinogenesis.
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http://dx.doi.org/10.31557/APJCP.2021.22.11.3647DOI Listing
November 2021

Evaluation of Phytochemicals and Bioactive Properties in Mangrove Associate . ex J.F.Gmel. of Indian Sundarbans.

Front Pharmacol 2021 10;12:584019. Epub 2021 Mar 10.

Department of Microbiology, Bose Institute, Kolkata, India.

Suaeda monoica Forssk. ex J.F.Gmel. (Amaranthaceae), a mangrove associate and ethno-medicinal herb of Indian Sundarbans, was investigated as a promising source of bioactive compounds. Various polar and nonpolar solvent extracts of the leaf and root-shoot parts of the plant exhibited antioxidant, antibacterial, antifungal, allelopathic, mosquitocidal, antihaemolytic and antidiuretic potential. Moreover, to meet pharmacological requirements, the antioxidant ability of the plant was validated by both chemical and biological analyses. Extraction yield and presence of different phytochemicals like phenolics, flavonoids, tannins and saponins were compared in various solvent-extracted fractions. Principle component analysis revealed that the antioxidant property present in different extracts maintained a positive correlation with the occurrence of polyphenols (phenolics, tannins and flavonoids). Biochemical evaluation, HPLC examination and GC-MS analysis showed a differential level of the presence of various phytochemicals in different solvent extracts. In contrast to mosquitocidal, antioxidant, antihaemolytic and phytotoxic properties which were observed to be dominant in polar solvent extracts, maximum antibacterial potency was detected in nonpolar -hexane fractions. Overall, the plant extract is nontoxic in nature and a dose amounting to 3,000 mg/kg was well tolerated by Swiss albino mice. A combination of HPLC and GC-MS analyses showed the presence of a large number of structurally diverse phytochemicals, many of which had already been reported as insecticidal, mosquitocidal, antibacterial, herbicidal, antidiuretic, antioxidant and anti-haemolytic compounds. All these findings support that the least explored traditional edible medicinal mangrove associate S.monoica is enriched with multiple bioactive molecules and may be considered as one of the richest sources of various lead molecules of pharmaceutical importance.
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http://dx.doi.org/10.3389/fphar.2021.584019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006309PMC
March 2021

Curcumin Rescues Doxorubicin Responsiveness via Regulating Aurora a Signaling Network in Breast Cancer Cells.

Asian Pac J Cancer Prev 2021 Mar 1;22(3):957-970. Epub 2021 Mar 1.

Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, India.

Background: Insensitivity towards anthracycline drugs like doxorubicin poses a significant challenge in the treatment of breast cancer. Among several factors, Aurora A (a mitotic serine threonine kinase) plays crucial roles in acquiring non-responsiveness towards doxorubicin. However, the mechanisms underlying need to be elucidated. The present study was therefore designed to evaluate the underlying mechanisms of Aurora A mediated doxorubicin insensitivity in MCF-7Dox/R, an isolated resistant-subline of MCF-7 (breast adenocarcinoma cell line). Effect of curcumin, a natural phytochemical in restoring doxorubicin sensitivity by targeting Aurora A was assessed furthermore.

Methods: A doxorubicin resistant subline (MCF-7Dox/R) was isolated from the parental MCF-7 cells by treating the cell with gradual step-wise increasing concentration of the drug. Expressions of Aurora A and its target proteins (Akt, IκBα and NFκB) were assessed in both parental and MCF-7Dox/R cells. Both the cell lines were pretreated with curcumin prior to doxorubicin treatment. Cellular proliferation rate was measured using BrdU (5-bromo-2'-deoxyuridine) assay kit. Intracellular doxorubicin accumulation was estimated spectrofluorimetrically. Cellular uptake of curcumin (spectrophotometric and spectrofluorimetric method) and its nuclear localization was confirmed by confocal microscopic study. Protein expressions were determined by western blot analysis. Localization of Aurora A was ascertained by immunofluorescence assay. To explore the possible outcome of impact of curcumin on Aurora A, cell-cycle distribution and apoptosis were performed subsequently.

Results: Higher expressions of Aurora A in MCF-7Dox/R cells led to phosphorylation of Akt as well as IκBα. Phosphorylated IκBα preceded release of NFκB. Phospho-Akt, NFκB consequentially decreased doxorubicin accumulation by enhancing the expressions of ABCG2 and Pgp1 respectively. Curcumin by regulating Aurora A and its target molecules sensitized resistant subline towards doxorubicin mediated G2/M-arrest and apoptosis.

Conclusion: Molecular targeting of Aurora A by curcumin restores chemosensitivity by increasing the efficacy of doxorubicin in breast cancer.
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http://dx.doi.org/10.31557/APJCP.2021.22.3.957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286672PMC
March 2021

Comparison of Quality of Life and Bone Mass Density among Postmenopausal Women: A Cross-sectional Study.

J Midlife Health 2020 Oct-Dec;11(4):224-230. Epub 2021 Jan 21.

Department of Physical Medicine and Rehabilitation, King George's Medical University, Lucknow, Uttar Pradesh, India.

Background: Postmenopausal women are at highest risk of developing osteoporosis, since their bone mineral density is reduced due to decrease in estrogen level. Various other physiological, emotional, and psychological changes jeopardize the health of these vulnerable females in total and reduce their quality of life (QoL).

Aims And Objectives: To compare the QoL and bone mass density (BMD) among normal BMD, osteopenic, and osteoporotic postmenopausal women.

Setting And Design: A cross-sectional observational study was conducted in the outpatient department of physical medicine and rehabilitation at a tertiary care center of northern India from August 2019 to February 2020.

Materials And Methods: Baseline sociodemographic characteristics of all postmenopausal women were collected using a quantitative tool. Assessment of QoL was done by pretested and validated QUALEFFO-41 scale. For all the women, a bone mineral densitometry test was performed on the L1-L4 lumbar spine, femoral neck, and forearm by the dual-energy X-ray absorptiometry method.

Statistical Analysis: One-way ANOVA test was used to compare the mean BMD values across the three groups. Determination of predictive factors for QoL was performed using stepwise logistic regression analysis.

Results: Significant differences were noted for the mean values of the three domains, i.e., pain, physical, and social function ( < 0.01). Women with osteoporosis had significantly higher pain scores as compared to others. Among those with osteoporosis, the pain scores have significantly increased gradually as age increases.

Conclusion: Postmenopausal women with osteopenia and osteoporosis have poor QoL as compared to those with normal BMD.
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http://dx.doi.org/10.4103/jmh.JMH_107_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978055PMC
January 2021

Prevalence of with other co-infecting parasites in Barak Valley, Assam, India: a molecular approach.

J Parasit Dis 2019 Sep 9;43(3):426-442. Epub 2019 Apr 9.

2Department of Life Science and Bioinformatics, Assam University, Silchar, Assam India.

was included in the World Health Organization's Neglected Disease Initiative in 2004 as it may range from asymptomatic to chronic or severe diarrhoea and chronic disorders post-infection. The present study aimed to find out the rate of sole infection of and co-infection of this with other protozoan parasites among the inhabitants of Barak Valley region of Southern Assam by conventional and molecular detection. A total of 1168 samples were collected from different groups of individuals, all the collected samples were subjected to microscopy after specific staining by Lugol's iodine solution, Trichrome staining and modified ZN staining procedures. Microscopically positive samples were further confirmed by PCR using specific primer sets. Of the total no. of samples, 267 (22.85%) were positive by PCR for with a little higher rate of infection in female (24.06%) (OR = 1.2192, CI = 0.9262 to 1.6049) than male (21.27%). The rate of infection is comparatively higher (25.93%) in the age group of 0-5 years (OR = 1.9149, CI = 1.2558 to 2.9200). In 196 samples co-existence was observed and detected by PCR with some other protozoan parasites like spp., spp. and spp. The rate of infection was higher (31.96%) among the participants who collected water from river. Least of the participants showed diarrhoeal symptoms (18.18%) but majority (28.45%) complained for having abdominal cramps (OR = 1.3402, CI = 0.8815 to 1.7855). Among the human infective assemblages, assemblage specific molecular detection revealed the rate of infection of assemblage B was comparatively higher (60.30%) than assemblage A.
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http://dx.doi.org/10.1007/s12639-019-01107-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667524PMC
September 2019

Rhizobacteria of of Indian Sundarbans Promote Rice Growth Under Saline and Heavy Metal Stresses Through Exopolysaccharide Production.

Front Microbiol 2019 29;10:1207. Epub 2019 May 29.

Department of Microbiology, Bose Institute, Kolkata, India.

The species isolated from the rhizosphere of the true mangrove of Indian Sundarbans showed enhanced rice growth promotion under combined stress of salt and arsenic in pot assay. Interestingly, under abiotic stress conditions, sp. Exo1 was observed as an efficient producer of exopolysaccharide. The study revealed that salt triggered exopolysaccharide production, which in turn, increased osmotic tolerance of the strain. Again, like salt, presence of arsenic also caused increased exopolysaccharide production that in turn sequestered arsenic showing a positive feedback mechanism. To understand the role of exopolysaccharide in salt and arsenic biosorption, purified exopolysaccharide mediated salt and arsenic sequestration were studied both under and conditions and the substrate binding properties were characterized through FT-IR and SEM-EDX analyses. Finally, observation of enhanced plant growth in pot assay in the presence of the strain and pure exopolysaccharide separately, confirmed direct role of exopolysaccharide in plant growth promotion.
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http://dx.doi.org/10.3389/fmicb.2019.01207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549542PMC
May 2019

Characterization of plant growth promoting feature of a neutromesophilic, facultatively chemolithoautotrophic, sulphur oxidizing bacterium Delftia sp. strain SR4 isolated from coal mine spoil.

Int J Phytoremediation 2019 16;21(6):531-540. Epub 2019 Jan 16.

a Department of Biotechnology , Techno India University , Kolkata , WB , India.

A new facultative chemolithoautotrophic heavy metal resistant sulfur-oxidizing bacterium was isolated from spoil sample of an open cast coal mine. FESEM demonstrated that the bacterium from Delftia genus was rod-shaped mucoid and motile. It autotrophically oxidized 20 mM thiosulfate and 1 g l elemental sulfur to 220 mg l and 203 mg l of sulfate, respectively in 7 days under oxic condition and was also able to grow heterotrophically. The strain showed many plant growth promoting properties like production of IAA (23 ug ml), ammonia (6 umol ml), siderophore (55% siderophore unit), and HCN (30 ppm) upon 48 hours of incubation. In Pikovskaya's agar, the strain showed phosphate solubilization index of 2.0 and solubilized tri-calcium phosphate (232 ug ml) and lowered pH from 8.0 to 4.5 within 18 days. The strain yielded promising results on Brassica juncea growth and sulfur, phosphorus, and lead uptake. Where sulfur and phosphorous accumulation was 52 and 116% higher in whole treated plants (derived from microbe-coated seeds), lead accumulation were 81 and 50% higher in shoot and root of the treated plants than control plants (derived from untreated seeds) . These results point that this multifunctional strain can be proposed for phytorestoration of heavy metal contaminated sites.
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http://dx.doi.org/10.1080/15226514.2018.1537238DOI Listing
September 2019

Arsenic Bioremediation by Indigenous Heavy Metal Resistant Bacteria of Fly Ash Pond.

Bull Environ Contam Toxicol 2018 Oct 10;101(4):527-535. Epub 2018 Sep 10.

Department of Biotechnology, Techno India University, EM 4/1 Sector V, Salt Lake, Kolkata, West Bengal, 700091, India.

Fly ash (FA), the major by-product of coal-fired thermal power plants, causes significant environmental degradation owing to its injurious heavy metal contents. Leaching of arsenic (As) from ash ponds is especially significant as As released from FA can increase As concentration of drinking water above maximum contaminant level of 10 ppb. The aim of this paper was demonstration of As bioremediation potential of indigenous As resistant bacteria present in the weathered pond ash sample. Ten isolates belonging to Bacillus, Micrococcus, Kytococcus and Staphylococcus genera were characterized. Biochemical tests showed reduction of relatively non toxic arsenate to more toxic arsenite by two strains while four strains showed oxidation of arsenite to arsenate. Two exoplolysaccharide producing strains were shown to absorb As within their biomass. Total heterotrophs versus As resistant heterotrophs counting performed showed that FA was enriched with As resistant heterotrophs. Column leaching based microcosm study revealed overall As detoxification potential of the isolated microbes.
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http://dx.doi.org/10.1007/s00128-018-2428-zDOI Listing
October 2018

Characterization of a topologically unique oxygenase from Sphingobium sp. PNB capable of catalyzing a broad spectrum of aromatics.

Enzyme Microb Technol 2018 Apr 18;111:74-80. Epub 2017 Oct 18.

Department of Microbiology, Bose Institute, Kolkata 700054, India. Electronic address:

A Rieske non-heme iron ring-hydroxylating oxygenase (RHO) from Sphingobium sp. PNB involved in the initial oxidation of a wide range of low and high molecular weight polycyclic aromatic hydrocarbons (PAHs) was investigated. The RHO was shown to comprise of the gene products of distantly located ahdA1f-ahdA2f, ahdA3 and ahdA4 genes, which encoded the oxygenase α- and β-subunits, ferredoxin and reductase, respectively. In silico structural analysis of AhdA1f revealed a very large substrate-binding pocket, satisfying the spatial requirements to accommodate high molecular weight substrates. In addition, an atypical substrate access channel was noticed from the topology analysis of the oxygenase. Guided by molecular docking studies, dioxygenation of several PAHs as well as alkyl- and aryl benzenes was examined with the recombinant AhdA1fA2f expressed in Escherichia coli. Chromatographic and mass spectrometric analyses confirmed that AhdA1fA2f displays broad substrate specificity towards a wide range of aromatic hydrocarbons including potential xenobiotics, demonstrating metabolic robustness of strain PNB.
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http://dx.doi.org/10.1016/j.enzmictec.2017.10.006DOI Listing
April 2018

Identification of Chromium Resistant Bacteria from Dry Fly Ash Sample of Mejia MTPS Thermal Power Plant, West Bengal, India.

Bull Environ Contam Toxicol 2016 Feb 24;96(2):210-6. Epub 2015 Nov 24.

Department of Biotechnology, Techno India University, Salt Lake, Sector V, Kolkata, West Bengal, 700 091, India.

Eight chromium resistant bacteria were isolated from a dry fly ash sample of DVC-MTPS thermal power plant located in Bankura, West Bengal, India. These isolates displayed different degrees of chromate reduction under aerobic conditions. According to 16S rDNA gene analysis, five of them were Staphylococcus, two were Bacillus and one was Micrococcus. The minimum inhibitory concentration towards chromium and the ability to reduce hexavalent chromium to trivalent chromium was highest in Staphylococcus haemolyticus strain HMR17. All the strains were resistant to multiple heavy metals (As, Cu, Cd, Co, Zn, Mn, Pb and Fe) and reduced toxic hexavalent chromium to relatively non toxic trivalent chromium even in the presence of these multiple heavy metals. All of them showed resistance to different antibiotics. In a soil microcosm study, S. haemolyticus strain HMR17 completely reduced 4 mM hexavalent chromium within 7 days of incubation.
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http://dx.doi.org/10.1007/s00128-015-1692-4DOI Listing
February 2016

Phenethyl isothiocyanate, by virtue of its antioxidant activity, inhibits invasiveness and metastatic potential of breast cancer cells: HIF-1α as a putative target.

Free Radic Res 2016 7;50(1):84-100. Epub 2015 Dec 7.

a Department of Environmental Carcinogenesis & Toxicology , Chittaranjan National Cancer Institute , Kolkata , West Bengal , India ;

Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in facilitating tumor progression and metastasis. Reducing the levels of HIF-1α might therefore be an important anticancer strategy. This could be achieved by understanding the key cellular events involved in HIF-1α activation. Present study explored the effect of phenethyl isothiocyanate (PEITC), a natural isothiocyanate, found in cruciferous vegetables on the expression of HIF-1α and HSP90 in breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) under both normoxia and hypoxia. This study established the possible role of ROS in the up-regulation of these markers in breast cancer cells. PEITC-induced nuclear accumulation of Nrf2, increased the activities of several antioxidant enzymes, and thus reduced the ROS burden of the tumor cells by acting as an indirect antioxidant. This resulted in the down-regulation of HSP90 and thereby HIF-1α expression. HSP90 was also found to be involved in the regulation of HIF-1α. A probable link between down-regulation of HIF-1α with reduction of ROS by PEITC through induction of Nrf2 was determined. Finally, our study demonstrated that modulation of HIF-1α by PEITC retarded adhesion, aggregation, migration and invasion of the breast cancer cells, thereby showing anti-metastatic effect. Activities of MMPs (2 & 9) and expression of VEGF were also altered by PEITC.
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http://dx.doi.org/10.3109/10715762.2015.1108520DOI Listing
October 2016

Inhibition of crosstalk between Bcr-Abl and PKC signaling by PEITC, augments imatinib sensitivity in chronic myelogenous leukemia cells.

Chem Biol Interact 2015 Dec 9;242:195-201. Epub 2015 Oct 9.

Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, 37, S P Mukherjee Road, Kolkata, 700 026, India.

Chronic myelogenous leukemia (CML), a clonal hyperproliferation of immature blood cells accounts for 20% of adult leukemia cases. Reciprocal translocation of chromosomes 9 and 22, results into Bcr-Abl fusion and is responsible for expression of a tyrosine kinase protein p210(bcr/abl), which mediates several survival pathways and confer therapeutic resistance. Protein kinase C (PKC), a family of serine threonine kinases play an important role in the process of leukemogenesis. A crosstalk between Bcr-Abl and PKC signaling has been documented. Therefore, targeting p210(bcr/abl) and its associated signaling proteins using non-toxic natural means will be an effective strategy for antileukemic therapy. Aim of the present study is to investigate whether PEITC, a natural isothiocyanate in combination with imatinib mesylate (IM), a tyrosine kinase inhibitor could increase the therapeutic efficacy of IM by modulating the expression of p210(bcr/abl). Enhanced cytotoxic efficacy of IM by PEITC was further validated using another myelogenous leukemia cell line, KU812. It was observed that PEITC in combination with IM efficiently downregulated the expression of p210(bcr/abl) in chronic myelogenous leukemia cell lines (K-562). PEITC inhibited the expressions of PKCα, PKCβII and PKCζ (both phosphorylated and total form). Expression of Raf1 and ERK1/2, two important target proteins in PKC signaling cascade was diminished. The result indicated that PEITC ultimately reduced expression of Raf1 and ERK1/2 through Bcr-Abl and PKC inhibition. This result was further confirmed by UCN-01, a selective PKC inhibitor and IM; indicating an association between p210(bcr/abl) and PKC with Raf1 and ERK1/2. PEITC thus may have enormous potential in synergistic therapy of leukemia by enhancing drug efficacy.
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http://dx.doi.org/10.1016/j.cbi.2015.10.004DOI Listing
December 2015

Molecular and genetic basis of depression.

J Genet 2014 Dec;93(3):879-92

Department of Zoology, Banaras Hindu University, Varanasi 221 005, India.

Joyousness or sadness is normal reaction to state of life. If any of these lead to certain semi-permanent changes in daily life, then it is termed as mental disorder. Depression is one of the mental disorders with a state of low mood and aversion to activities that exerts a negative effect on a person's thoughts and behaviour. Adolescent group is probably the world's largest active group of people, who are getting prone to this state of mind leading to their diminished mental and physical abilities. Depression is closely linked to stress and thus a chronic stressful life can increase the risk of depression. Depression is a complex disease having both genetic and environmental components as contributing factors. In this study an attempt has been made to put forward the understanding of the known genes and their functional relationships with depression and stress with special reference to BDNF and 5-HTTLPR. Analysis of common genetic variants associated with depression, especially in the members of a family who had a previous history, might help in identifying the individuals at risk prior to the onset of depression.
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http://dx.doi.org/10.1007/s12041-014-0449-xDOI Listing
December 2014

Integrated phytobial remediation for sustainable management of arsenic in soil and water.

Environ Int 2015 Feb 3;75:180-98. Epub 2014 Dec 3.

Techno India University, Salt Lake, Kolkata 700091, India.

Arsenic (As), cited as the most hazardous substance by the U.S. Agency for Toxic Substance and Disease Registry (ATSDR, 2005), is an ubiquitous metalloid which when ingested for prolonged periods cause extensive health effects leading to ultimate untimely death. Plants and microbes can help mitigate soil and groundwater As problem since they have evolved elaborate detoxification machineries against this toxic metalloid as a result of their coexistence with this since the origin of life on earth. Utilization of the phytoremediation and bioremediation potential of the plants and microbes, respectively, is now regarded as two innovative tools that encompass biology, geology, biotechnology and allied sciences with cutting edge applications for sustainable mitigation of As epidemic. Discovery of As hyperaccumulating plants that uptake and concentrate large amounts of this toxic metalloid in their shoots or roots offered new hope to As phytoremediation, solar power based nature's own green remediation. This review focuses on how phytoremediation and bioremediation can be merged together to form an integrated phytobial remediation which could synergistically achieve the goal of large scale removal of As from soil, sediment and groundwater and overcome the drawbacks of the either processes alone. The review also points to the feasibility of the introduction of transgenic plants and microbes that bring new hope for more efficient treatment of As. The review identifies one critical research gap on the importance of remediation of As contaminated groundwater not only for drinking purpose but also for irrigation purpose and stresses that more research should be conducted on the use of constructed wetland, one of the most suitable areas of application of phytobial remediation. Finally the review has narrowed down on different phytoinvestigation and phytodisposal methods, which constitute the most essential and the most difficult part of pilot scale and field scale applications of phytoremediation programs.
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http://dx.doi.org/10.1016/j.envint.2014.11.010DOI Listing
February 2015

Curcumin augments the efficacy of antitumor drugs used in leukemia by modulation of heat shock proteins via HDAC6.

J Environ Pathol Toxicol Oncol 2014 ;33(3):247-63

Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India.

Heat shock proteins (HSPs) and histone deacetylase 6 (HDAC6) are induced under oxidative stress, which promotes oncogenesis. HSPs are regulated by heat shock factor1 (HSF1). HDAC6, a class IIb deacetylase, plays an essential role in tumorigenesis and cell stress response. HSPs, HSF1 and HDAC6 are up-regulated in cancer. In the present study, we explored the effect of curcumin, a phytochemical, on HSPs (27, 70, 90), HSF1 and HDAC6 in two different leukemia cell lines (K-562 and HL-60). The association between HDAC6, HSPs, and intrinsic oxidative stress was also investigated. Overexpression of HSPs (27, 70, 90), HSF1, and HDAC6 in leukemia cells were down-regulated by curcumin, and the effects on HSPs 27and 70 were less than that on HSP 90. This resulted in cell cycle arrest at the G2/M stage, leading to apoptosis. Different cell cycle regulatory proteins (p53, p21, cyclin B1, CDK1, Cdc25C) and some apoptosis-related proteins (Bcl-2, Bax, Bid, Bad, Apaf1, AIF and Cyt c) were altered by curcumin. Increased ROS levels in leukemia cells were quenched by curcumin. A probable association between high ROS level and the overexpression of the tumor markers was established in this study. Thus, curcumin enhanced the efficacy of anti-tumor drugs imatinib-mesylate and cytarabine through the inhibition of the tumor markers.
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http://dx.doi.org/10.1615/jenvironpatholtoxicoloncol.2014010913DOI Listing
November 2014

In search of natural remediation for cervical cancer.

Anticancer Agents Med Chem 2015 ;15(1):57-65

Chittaranjan National Cancer Institute, 37, S P Mukherjee Road, Kolkata 700026, India.

Cancer is a serious global health issue. Cancer of the cervix is one of the leading gynecological malignancies worldwide; though it is more prevalent in the developing countries. Fruitful approaches are needed to control cervical cancer. Awareness through proper education, screening and early detection may pave a way to combat the disease process in the first place. Surgery, chemotherapy and radiotherapy are some of the common modes of treatment for cervical cancer. Conventional medical treatments often are not able to eliminate the offending growth fully and are not free from complications. Side effects very often are disastrous. Therefore, it is high time to focus our attention to bring about a novel way to tackle the problem. Advocating holistic approach using plant derived phytochemicals may address this health problem. These molecules show potent anticancer potential and are free from toxicity. Adjunctive therapies using phytochemicals may prove to be of tremendous importance. Plants are a prime source of effective drugs for the treatment of various forms of cancer. Many of these compounds are well characterized and have led the researchers to develop potential chemotherapeutic agents. Neutraceuticals may not replace the conventional treatment regimen, but they may enhance the efficacy of chemotherapy and radiotherapy.
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http://dx.doi.org/10.2174/1871520614666140722084154DOI Listing
August 2015

Functional characterization of diverse ring-hydroxylating oxygenases and induction of complex aromatic catabolic gene clusters in Sphingobium sp. PNB.

FEBS Open Bio 2014 7;4:290-300. Epub 2014 Mar 7.

Department of Microbiology, Bose Institute, P-1/12 C.I.T. Scheme VII M, Kolkata 700054, India.

Sphingobium sp. PNB, like other sphingomonads, has multiple ring-hydroxylating oxygenase (RHO) genes. Three different fosmid clones have been sequenced to identify the putative genes responsible for the degradation of various aromatics in this bacterial strain. Comparison of the map of the catabolic genes with that of different sphingomonads revealed a similar arrangement of gene clusters that harbors seven sets of RHO terminal components and a sole set of electron transport (ET) proteins. The presence of distinctly conserved amino acid residues in ferredoxin and in silico molecular docking analyses of ferredoxin with the well characterized terminal oxygenase components indicated the structural uniqueness of the ET component in sphingomonads. The predicted substrate specificities, derived from the phylogenetic relationship of each of the RHOs, were examined based on transformation of putative substrates and their structural homologs by the recombinant strains expressing each of the oxygenases and the sole set of available ET proteins. The RHO AhdA1bA2b was functionally characterized for the first time and was found to be capable of transforming ethylbenzene, propylbenzene, cumene, p-cymene and biphenyl, in addition to a number of polycyclic aromatic hydrocarbons. Overexpression of aromatic catabolic genes in strain PNB, revealed by real-time PCR analyses, is a way forward to understand the complex regulation of degradative genes in sphingomonads.
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http://dx.doi.org/10.1016/j.fob.2014.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048848PMC
June 2014

Reversal of resistance towards cisplatin by curcumin in cervical cancer cells.

Asian Pac J Cancer Prev 2014 ;15(3):1403-10

Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata, India E-mail :

Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone SiHaR (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and SiHaR, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in SiHaR due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.
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http://dx.doi.org/10.7314/apjcp.2014.15.3.1403DOI Listing
November 2014

Targeting heat shock proteins by phenethyl isothiocyanate results in cell-cycle arrest and apoptosis of human breast cancer cells.

Nutr Cancer 2013 ;65(3):480-93

Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Kolkata, India.

Heat shock proteins (HSPs) are chaperones for several client proteins involved in transcriptional regulation, signal transduction, and cell cycle control. HSPs (27, 70, and 90) are abundantly expressed in a wide range of cancers and are transcriptionally regulated by heat shock factor (HSF1). Most of the synthetic HSP inhibitors exhibit toxicity, therefore, searching for inhibitors with limited or no toxicity will be of help. The objective of the present study was to determine the effect of natural isothiocyanate (phenethyl isothiocyanate; PEITC) on different HSPs (27, 70, and 90) and HSF1 in 2 breast cancer cell lines, namely breast adenocarcinoma MCF-7 (with wild type p53) and highly metastatic breast cancer cell MDA-MB-231 (with mutated p53). PEITC significantly inhibited the expression of HSPs (particularly HSP 90) and HSF1. Molecular consequences due to HSP inhibition were downregulation of cell-cycle regulatory proteins like Cyclin B1, CDK1, Cdc25C, PLK-1, and upregulation of p21 irrespective of p53 status. These modulations were accompanied by cell-cycle arrest at G2/M phase and apoptosis by activation of caspases 3 and 9. PEITC therefore may be regarded as a potent HSP inhibitor and an antitumor agent in the treatment of breast cancer.
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http://dx.doi.org/10.1080/01635581.2013.767366DOI Listing
September 2013

Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast cancer cells by targeting heat shock proteins.

Biochem Biophys Res Commun 2012 Oct 10;427(1):80-5. Epub 2012 Sep 10.

Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700 026, India.

Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport and/or stabilization by acting as a molecular chaperone, leading to inhibition of apoptosis by both caspase dependent and/or independent pathways. HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion and metastasis. HSPs particularly 27, 70, 90 and the transcription factor heat shock factor1 (HSF1) play key roles in the etiology of breast cancer and can be considered as potential therapeutic target. The present study was designed to investigate the role of sulphoraphane, a natural isothiocyanate on HSPs (27, 70, 90) and HSF1 in two different breast cancer cell lines MCF-7 and MDA-MB-231 cells expressing wild type and mutated p53 respectively, vis-à-vis in normal breast epithelial cell line MCF-12F. It was furthermore investigated whether modulation of HSPs and HSF1 could induce apoptosis in these cells by altering the expressions of p53, p21 and some apoptotic proteins like Bcl-2, Bax, Bid, Bad, Apaf-1 and AIF. Sulphoraphane was found to down-regulate the expressions of HSP70, 90 and HSF1, though the effect on HSP27 was not pronounced. Consequences of HSP inhibition was upregulation of p21 irrespective of p53 status. Bax, Bad, Apaf-1, AIF were upregulated followed by down-regulation of Bcl-2 and this effect was prominent in MCF-7 than in MDA-MB-231. However, very little change in the expression of Bid was observed. Alteration in Bcl-2 Bax ratio resulted in the release of cytochrome c from mitochondria and activation of caspases 3 and 9 which are in agreement with apoptotic index values. Sulphoraphane therefore can be regarded as a potent inducer of apoptosis due to HSP modulation in breast cancer cells.
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http://dx.doi.org/10.1016/j.bbrc.2012.09.006DOI Listing
October 2012

meta-Cleavage of hydroxynaphthoic acids in the degradation of phenanthrene by Sphingobium sp. strain PNB.

Microbiology (Reading) 2012 Mar 22;158(Pt 3):685-695. Epub 2011 Dec 22.

Department of Microbiology, Bose Institute, P-1/12 C.I.T. Scheme VII M, Kolkata, West Bengal, India.

Polycyclic aromatic hydrocarbons (PAHs) comprise a group of priority organic pollutants that are toxic and/or carcinogenic. Phenanthrene, the simplest PAH among recognized priority pollutants, is commonly used as a model compound for the study of PAH biodegradation. Sphingobium sp. strain PNB, capable of degrading phenanthrene as a sole carbon and energy source, was isolated from a municipal waste-contaminated soil sample. A combination of chromatographic and spectrometric analyses, together with oxygen uptake and enzyme activity studies, suggested the presence of phenanthrene degradation pathways in this strain. Identification of metabolites suggested that initial dioxygenation of phenanthrene took place at both 3,4- and 1,2-carbon positions; meta-cleavage of resultant diols led to the formation of 1-hydroxy-2-naphthoic acid and 2-hydroxy-1-naphthoic acid, respectively. The hydroxynaphthoic acids, in turn, were metabolized by a meta-cleavage pathway(s), leading to the formation of 2,2-dicarboxychromene and 2-hydroxychromene-2-glyoxylic acid, respectively. These metabolites were subsequently transformed to catechol via salicylic acid, which further proceeds towards the tricarboxylic acid cycle leading to complete mineralization of the compound phenanthrene. The present study establishes the metabolism of hydroxynaphthoic acids by a meta-cleavage pathway in the degradation of phenanthrene, expanding our current understanding of microbial degradation of PAHs.
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http://dx.doi.org/10.1099/mic.0.053363-0DOI Listing
March 2012

Antagonistic role of tea against sodium arsenite-induced oxidative DNA damage and inhibition of DNA repair in Swiss albino mice.

J Environ Pathol Toxicol Oncol 2011 ;30(4):311-22

Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata, India.

Arsenic (As) contamination in groundwater is of increasing health concern in West Bengal, India. Arsenic has been associated with various human cancers, but the precise mechanism of its co-carcinogenic action is not clearly elucidated. Oxidative stress and defective repair mechanisms may promote accumulation of mutations and may be a stepping stone for carcinogenesis. Prevention of arsenic-induced oxidative stress and repair inhibition may reduce the chances of initiation of cancer. Tea polyphenols are reported to have excellent chemopreventive properties against cancer. This study aimed to elucidate the role of tea against arsenic-induced formation of 8-hydroxy-2'-deoxyguanosine (8OHdG) and arsenic-suppressed DNA repair in Swiss albino mice. Both green and black tea gave fruitful results in the reduction of 8OHdG and 8-oxoguanine DNA glycosylase (OGG1) in Swiss albino mice administered sodium arsenite (As III). DNA repair enzymes--such as PARP1, DNA β-polymerase, XRCC1, DNA ligase III, DNA protein kinase (catalytic subunit), XRCC 4, DNA ligase IV, and DNA topoisomerase IIβ--were induced by the phytochemicals at both the protein and genetic levels. Thus, tea polyphenols may prove effective in treating arsenic-induced carcinogenesis.
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http://dx.doi.org/10.1615/jenvironpatholtoxicoloncol.v30.i4.40DOI Listing
February 2012

Curcumin prevents DNA damage and enhances the repair potential in a chronically arsenic-exposed human population in West Bengal, India.

Eur J Cancer Prev 2011 Mar;20(2):123-31

Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata, West Bengal, India.

Induction of oxidative stress and inhibition of DNA repair are possible modes of arsenic-induced carcinogenesis. In West Bengal, India, several districts contain high levels of arsenic, which are far above the WHO-recommended standard. Prevention of arsenic-induced oxidative stress and induction of repair enzymes by curcumin, an active ingredient of turmeric, may be an effective strategy to combat the adverse effects of arsenic. This study aimed at observing the role of curcumin in reducing 8-hydroxy-20-deoxyguanosine formation and enhancing DNA repair capacity in the arsenic-exposed population of West Bengal. Chronically arsenic-exposed volunteers (n= 66), who were asymptomatic, were selected for this study. Our results indicated that curcumin suppressed the 8-hydroxy-20-deoxyguanosine level and OGG1 expression, which were increased by arsenic. Curcumin also induced DNA repair enzymes involved in both base excision repair and nonhomologous end-joining pathways. In this study, both the protein expression and genetic profile were observed for poly-ADP-ribose polymerase 1, DNA b polymerase, X ray repair cross complement 1, DNA ligase III, DNA protein kinase catalytic sub-unit, X ray repair cross-complement 4, DNA ligase IV, and topoisomerase II b. The results indicated that arsenic-inhibited DNA repair was induced by curcumin, both at protein and genetic levels. Thus, curcumin intervention may be a useful modality for the prevention of arsenic-induced carcinogenesis.
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http://dx.doi.org/10.1097/cej.0b013e328341017aDOI Listing
March 2011

Cloning and characterization of a p-cymene monooxygenase from Pseudomonas chlororaphis subsp. aureofaciens.

Res Microbiol 2010 Dec 28;161(10):876-82. Epub 2010 Oct 28.

Department of Microbiology, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata 700054, India.

p-Cymene monooxygenase is the enzyme system that catalyzes the hydroxylation of p-cymene to 4-isopropylbenzyl alcohol (p-cumic alcohol), the initial step in the assimilation of p-cymene by Pseudomonas chlororaphis subsp. aureofaciens. Cloning and sequencing of single NADH-dependent cytochrome c reductase gene (cymA) present in P. chlororaphis subsp. aureofaciens was described earlier. In this study, analysis of the upstream sequence of cymA revealed two open reading frames, designated as cymB (495 bp) and cymM (1128 bp). Database searches with the cymM gene product showed similarity to integral-membrane di-iron enzymes, while that with cymB showed no significant similarity to other known proteins with the exception of epoxystyrene isomerases. Expression of all three components (cymMBA) in Escherichia coli confirmed its ability for p-cymene methyl group hydroxylation, while expression of cymM and cymA along with the partially truncated cymB gene showed an 85% decrease in the hydroxylation capacity. Our results suggest for the first time that the small protein, CymB, having no conserved domains in protein databases, is involved as enhancer/activator in p-cymene hydroxylation.
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http://dx.doi.org/10.1016/j.resmic.2010.10.008DOI Listing
December 2010

Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice.

Asian Pac J Cancer Prev 2010 ;11(1):239-47

Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.

Inorganic arsenic (As) is considered as a human carcinogen because it is associated with cancers of skin, lung, liver and bladder in exposed population. Consumption of As contaminated ground water for long term causes oxidative stress. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance results severe imbalance of the cellular antioxidant defense mechanism. The present study was conducted to investigate the antioxidative effect of curcumin against sodium arsenite (As III) induced oxidative damage in Swiss albino mice. Bio-monitoring with comet assay and micronucleus assay revealed that the increase in genotoxicity caused by As III was counteracted when mice were orally administered with 5, 10 and 15 mg curcumin kg-1 bw (body weight) daily. ROS generation, lipid peroxidation and protein carbonyl content, which were elevated by As III, were reduced when treated with curcumin. Curcumin also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the present work provides a direct evidence for the involvement of curcumin in reducing As III induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals.
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November 2010

Targeting protein kinase C (PKC) and telomerase by phenethyl isothiocyanate (PEITC) sensitizes PC-3 cells towards chemotherapeutic drug-induced apoptosis.

J Environ Pathol Toxicol Oncol 2009 ;28(4):269-82

Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Kolkata 700026, India.

Prostate cancer is the leading cause of cancer-related death in men, incidences of which are increasing gradually in India. Protein kinase C (PKC), an enzyme, gets overexpressed in prostate cancer and results in a resistance to chemotherapy. Telomerase, a reverse transcriptase, is highly activated in prostate cancer cells. Both of these enzymes can be considered as potential molecular markers for prostate cancer. The present study investigates the effects of natural isothiocyanate phenethyl isothiocyanate (PEITC) in modulating the activities of PKC and telomerase in the androgen-independent human prostate adenocarcinoma (PC-3) cell line. We observed that PEITC downregulated the antiapoptotic isoforms (PKC alpha and epsilon) efficiently and zeta moderately. Basal level of PKC delta, a proapoptotic form, was very poor and its modulation was not significant. PEITC also inhibited the activity of telomerase. Studies were conducted to measure the degree of apoptotic cell death induced either by PEITC alone or in combination with adriamycin or etoposide. Apoptosis was evident from the release of mitochondrial cytochrome c, apoptotic index, and by the induction of caspases 3 and 8. PEITC exhibited remarkable efficacy in sensitizing PC-3 cells to undergo cell death by adriamycin and etoposide, which might prove to be of considerable value in synergistic therapy of cancer.
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http://dx.doi.org/10.1615/jenvironpatholtoxicoloncol.v28.i4.30DOI Listing
February 2010

Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal.

Hum Exp Toxicol 2010 Jun 7;29(6):513-24. Epub 2010 Jan 7.

Chittaranjan National Cancer Institute, Kolkata, India.

Groundwater arsenic contamination has been a health hazard for West Bengal, India. Oxidative stress to DNA is recognized as an underlying mechanism of arsenic carcinogenicity. A phytochemical, curcumin, from turmeric appears to be potent antioxidant and antimutagenic agent. DNA damage prevention with curcumin could be an effective strategy to combat arsenic toxicity. This field trial in Chakdah block of West Bengal evaluated the role of curcumin against the genotoxic effects of arsenic. DNA damage in human lymphocytes was assessed by comet assay and fluorescence-activated DNA unwinding assay. Curcumin was analyzed in blood by high performance liquid chromatography (HPLC). Arsenic induced oxidative stress and elucidation of the antagonistic role of curcumin was done by observation on reactive oxygen species (ROS) generation, lipid peroxidation and protein carbonyl. Antioxidant enzymes like catalase, superoxide dismutase, glutathione reductase, glutathioneS-transferase, glutathione peroxidase and non-enzymatic glutathione were also analyzed. The blood samples of the endemic regions showed severe DNA damage with increased levels of ROS and lipid peroxidation. The antioxidants were found with depleted activity. Three months curcumin intervention reduced the DNA damage, retarded ROS generation and lipid peroxidation and raised the level of antioxidant activity. Thus curcumin may have some protective role against the DNA damage caused by arsenic.
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http://dx.doi.org/10.1177/0960327109359020DOI Listing
June 2010

Isothiocyanates sensitize the effect of chemotherapeutic drugs via modulation of protein kinase C and telomerase in cervical cancer cells.

Mol Cell Biochem 2009 Oct 12;330(1-2):9-22. Epub 2009 Apr 12.

Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, 700 026, India.

Isothiocyanates have potential chemopreventive and antitumor effects. In the present study, we examined the actions of PEITC and sulphoraphane in modulating the activity of protein kinase C (PKC) and telomerase in cervical cancer cell line HeLa. These tumor markers are highly activated in human cancers. These compound efficiently downregulated the antiapoptotic isoforms (PKC-alpha, -betaII, -epsilon, and -zeta) as well as telomerase, whereas the proapoptotic form (PKC-delta) was upregulated. Studies were performed to measure the degree of apoptotic cell death induced by either isothiocyanates alone, or in combination with adriamycin or etoposide. Apoptosis was evident from mitochondrial cytochrome c release, apoptotic index and caspases 3 and 8 activation. Results showed that pretreatment exhibited better efficacy in sensitizing HeLa cells toward apoptosis by modulating PKCs, telomerase. This effect of isothiocyanates might prove to be of considerable value in synergistic therapy of cancer such that the drug dose level could be minimized.
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http://dx.doi.org/10.1007/s11010-009-0095-4DOI Listing
October 2009

Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.

Life Sci 2009 Feb 3;84(7-8):194-204. Epub 2008 Dec 3.

Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata-700 026, India.

Aims: The tumor inhibiting property of green tea polyphenol epigallocatechin-3-gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases (MMPs) play pivotal roles in tumor invasion through degradation of basement membranes and extracellular matrix (ECM). We studied the effect of EGCG on matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion and signaling molecules that might be involved in the regulation of MMP-2 in human breast cancer cell line, MCF-7.

Main Methods: MCF-7 was treated with EGCG (20 muM, 24 h), the effect of EGCG on MMP-2 expression, activity and its regulatory molecules were studied by gelatin zymography, Western blot, quantitative and semi-quantitative real time RT-PCR, immunoflourescence and cell adhesion assay.

Key Findings: EGCG treatment reduced the activity, protein expression and mRNA expression level of MMP-2. EGCG treatment reduced the expression of focal adhesion kinase (FAK), membrane type-1-matrix metalloproteinase (MT1-MMP), nuclear factor-kappa B (NF-kB), vascular endothelial growth factor (VEGF) and reduced the adhesion of MCF-7 cells to ECM, fibronectin and vitronectin. Real time RT-PCR revealed a reduced expression of integrin receptors alpha5, beta1, alphav and beta3 due to EGCG treatment.

Significance: Down regulation of expression of MT1-MMP, NF-kB, VEGF and disruption of functional status of integrin receptors may indicate decreased MMP-2 activation; low levels of FAK expression might indicate disruption in FAK-induced MMP-2 secretion and decrease in activation of phosphatidyl-inositol-3-kinase (PI-3K), extracellular regulated kinase (ERK) indicates probable hindrance in MMP-2 regulation and induction. We propose EGCG as potential inhibitor of expression and activity of pro-MMP-2 by a process involving multiple regulatory molecules in MCF-7.
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http://dx.doi.org/10.1016/j.lfs.2008.11.018DOI Listing
February 2009
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