Publications by authors named "Azadeh Mahnam"

6 Publications

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TSGA10 Over Expression Decreases Metastasic and Metabolic Activity by Inhibiting HIF-1 in Breast Cancer Cells.

Arch Med Res 2020 01 18;51(1):41-53. Epub 2020 Feb 18.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical sciences, Kermanshah, Iran; Department of Molecular Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background And Aims: HIF-1 is an important factor that play critical roles in metabolic and metastasis activity of cancer cells. HIF-1 activity can have regulated by TSGA10. Although decreased metastatic activity of cancer cells through TSGA10 inhibitory effect on HIF-1 have already been demonstrated, changes in cancer metabolism and its impact on metastasis in breast cancer is still not determined. So, we aimed to investigate TSGA10 overexpression effect on breast cancer metabolism as well as metastasis.

Methods: TSGA10 vector was designed and stable transfected into MCF-7 cells. The efficiency of transfection was assessed by Real-time PCR and western blot. After HIF-1 induction at high and low glucose conditions, cell proliferation, cell cycle profile, metabolic and metastasis activity of cells were assessed. Furthermore, biomarker expressions of ER, PR, HER2, Ki67 and E-cadherin in cancer cells were measured.

Results: Our results showed decrease of cell proliferation and cell cycle arrest in G2/M phase. Reduce expression of GLUT1, lactate production and reactive oxygen species (ROS) below their basal level indicated decreased metabolic activity. Furthermore, metastatic activity reduction was shown by decrease expression of different involve genes in metastasis, protelytic activity of MMOLP-2/9, carbonic anhydrase (CA) IX activity and increase of wound closure. Moreover, except for E-cadherin, expression of ER, PR, HER2 and Ki67 was declined in cells.

Conclusion: Our findings indicated that TSGA10 overexpression could decrease the metastatic and metabolic activity of cancer cells through its inhibitory effect on HIF-1 activity. Therefore, TSGA10 could be considered in the research for therapeutic candidates in cancer.
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http://dx.doi.org/10.1016/j.arcmed.2019.12.002DOI Listing
January 2020

TSGA10 overexpression inhibits angiogenesis of HUVECs: A HIF-2α biased perspective.

Microvasc Res 2020 03 5;128:103952. Epub 2019 Nov 5.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Molecular Medicine Department, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Testis-specific gene antigen 10 (TSGA10) is a protein overexpressed in most cancers; except for some certain types where its expression is reduced. TSGA10 overexpression in HeLa cells has been shown to disrupt hypoxia inducible factor-1α (HIF-1α) axis and exert potent inhibitory effects. Since HIF-1α is structurally and biochemically similar to HIF-2α, TSGA10 is expected to bind HIF-2α and inhibit its function as well. This study elucidated that increased expression of TSGA10 in manipulated human umbilical vein endothelial cells (HUVECs) decreased the proliferation and migration of these cells as affirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and wound healing tests, respectively. It also inhibited in vitro angiogenesis of these cells in 3D collagen-cytodex model. Expression levels of genes controlled by HIF-2α including autocrine vascular endothelial growth factor (VEGF) were also assessed using real-time PCR. Our bioinformatic analysis also showed that TSGA10 could bind HIF-2α. Moreover, flow cytometry results indicated a cell cycle arrest in G2/M. Therefore, this study showed that overexpression of TSGA10, as a tumor suppressor gene, in endothelial cells resulted in decreased proliferation, migration and therefore, angiogenic activity of HUVECs. Since angiogenesis is vital for tumor development and metastasis, our findings could be of clinical significance in cancer therapy.
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http://dx.doi.org/10.1016/j.mvr.2019.103952DOI Listing
March 2020

Comparative in vitro/theoretical studies on the anti-angiogenic activity of date pollen hydro-alcoholic extract: Highlighting the important roles of its hot polyphenols.

Bioimpacts 2018 14;8(4):281-294. Epub 2018 Jun 14.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Date palm pollen (DPP) is the male reproductive soft powder from date flowers widely used as the valuable dietary supplement to fortify the size of testis and ovarian to increase the power of sex. This part of date palm significantly exhibited anti-diabetic, anti-inflammation and protective effects against male and female infertility. Though the anticancer activity of date fruits was previously reported, the DPP anti-angiogenic effects were not reported, and as the first study, its inhibitory effects were examined in the current study. The DPP soft powder was collected to prepare its hydro-alcoholic extract to examine its anti-angiogenic activity in an model. At different concentrations, the cytotoxicity of the prepared extract was examined on human umbilical vein endothelial cells (HUVECs) using lactate dehydrogenase method. Cell proliferation was determined using the MTT assay and cytodex-3D model in collagen gel was used to assay its possible anti-angiogenic activity. The expression of VEGF, and genes was measured using real-time polymerase chain reaction (PCR). Finally, molecular docking simulation was used to highlight the possible role of DPP polyphenols to interact with the associated receptors. The prepared hydro-alcoholic extract exhibited significant anti-angiogenic activity in a dose-dependent manner and decreased the endothelial cell proliferation. The calculated IC value for the examined extract in angiogenesis model was 260 µg·mL, respectively. Also, the expression of VEGF, and genes were significantly decreased. Docking simulation results unveiled that the isolated DPP polyphenols have the affinity to interact with ctDNA, VEGF and its receptors. The DPP is the new source of non-toxic anti-cancer agents to use as a dietary supplement in the pre-treatment of cancer.
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http://dx.doi.org/10.15171/bi.2018.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209826PMC
June 2018

The effect of , , and polymorphism in patients under warfarin therapy in city of Kermanshah.

Res Pharm Sci 2018 Aug;13(4):377-384

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

Polymorphism in the genes encoding enzyme and reductase significantly influence warfarin dose requirement since patients with , and mutant alleles require lower warfarin maintenance doses. Studies have reported the ethnic variations in the frequency of these genes within the various populations in Iran and other parts of the world. However, no such study has been done yet on Kurdish population in Kermanshah. From Kurdish population of Kermanshah province in Iran, a total of 110 patients who had heart surgery and taking warfarin, were genotyped for polymorphisms of , , and . Polymorphism genotyping was performed by sequencing as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes of and , respectively. The frequencies of -1639 GG, GA, and AA genotypes were 42%, 36%, and 22%, respectively and for 1*/1*, 1*/2*, 2*/2*, 1*/3*, 3*/3*, 2*/3* were 71%, 17%, 5.4%, 1.8%, 4.5%, and 0%, respectively. The frequency of -1639A allele was 42.3% and the frequencies of and *3 alleles were 14% and 5.4%, respectively. It was indicated that low warfarin dose requirements are strongly associated with the presence of and variant alleles. Our results confirmed the supply to understand the distribution of genomic biomarkers related to the drugs metabolism for future planning health programs.
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http://dx.doi.org/10.4103/1735-5362.235165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040167PMC
August 2018

Anti-angiogenic potential of trypsin inhibitor purified from Cucumis melo seeds: Homology modeling and molecular docking perspective.

Int J Biol Macromol 2017 Mar 10;96:118-128. Epub 2016 Dec 10.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Melons have a good source of protease inhibitors. Its fruit and seeds have been used as a traditional medicine. However, its effects on angiogenesis and mechanism of its action remain elusive. Herein trypsin inhibitor from aqueous extract of C. melo seeds (TICMS) was purified. Its effects on different steps of angiogenesis were evaluated. Also, we examined its effects on migration and angiogenesis of endothelial cells. Three dimensional model of TICMS protein was accurately built in which TICMS docked to αβ integrin and VEGFR1. Electrophoresis analysis of the purified protein revealed a single band with a molecular mass of about 3kDa. Treatment with TICMS at six doses resulted in a significant decrease of endothelial cell proliferation with an IC value of about 20μg/ml. Tubulogenesis assay revealed that a dose dependent anti-angiogenic activity of TICMS (5-40μg/ml). Also, TICMS had inhibitory effects on VEGF, MMP-2 and MMP-9 secretion. Our docking result speculated that TICMS could bind to the cleft between the αβ integrin and it able to decrease the activity of this receptor. The TICMS was also able to interact with VEGFR1 receptor, but with low probability. Based on our study, TICMS could be used as a specific angiogenesis inhibitor.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.12.027DOI Listing
March 2017

In vitro inhibition of angiogenesis by hydroalcoholic extract of oak (Quercus infectoria) acorn shell via suppressing VEGF, MMP-2, and MMP-9 secretion.

Pharm Biol 2013 Mar 8;51(3):361-8. Epub 2012 Nov 8.

Medical Biology Research Center and Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Context: Angiogenesis is an essential factor for cancer progression. Although more attention is paid in angiogenesis on its role in cancer biology, many other non-neoplastic diseases are also angiogenic-dependent. Recently, there is motivation to control cancer via inhibition of angiogenesis.

Objective: Quercus infectoria Olivier var (Fagaceae) (oak) is a plant whose different parts, such as its fruit shell, have been used extensively as a traditional drug in the west part of Iran. Although some biological properties of oak are determined, its effects on angiogenesis are unclear. So, we investigated the antiangiogenic effects of oak acorn shell.

Materials And Methods: Fresh oak acorns were collected, and after authentication; hydroalcoholic extract of acorn shells (5, 10, 20, 30, 40, 60, 80, and 100 μg/ml) was used for evaluation of its cytotoxicity, antiproliferative, and antiangiogenic effects in vitro. Also, effects of the extract on vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 secretion were assayed using enzyme-linked immunosorbent assay (ELISA) and gelatin zymography.

Results: Treatment with hydroalcoholic extract in eight doses resulted in a significant decrease of endothelial cell proliferation and angiogenesis with an IC₅₀ value of ~20 μg/ml, without any toxic effect. At 40 μg/ml, the extract inhibited MMP-9 activity; however, a dose-dependent reduction (60-80 µg/ml) in MMP-2 activity was seen. VEGF secretion was decreased with increase in the concentration of the extract from 5 to 100 μg/ml.

Discussion And Conclusion: This study indicated that hydroalcoholic extract of oak acorn shell acts as a potent antiangiogenic agent which exerts its inhibitory effect mainly through downregulation of essential mediators such as VEGF and MMPs.
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http://dx.doi.org/10.3109/13880209.2012.729147DOI Listing
March 2013