Publications by authors named "Hamid Ali Al-Jamal"

9 Publications

  • Page 1 of 1

Thymoquinone, as a Novel Therapeutic Candidate of Cancers.

Pharmaceuticals (Basel) 2021 Apr 16;14(4). Epub 2021 Apr 16.

Department of Biomedical Sciences, College of Health sciences, QU Health, Qatar University, Doha 2713, Qatar.

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of , TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.
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http://dx.doi.org/10.3390/ph14040369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074212PMC
April 2021

Thymoquinone Suppresses Cell Proliferation and Enhances Apoptosis of HL60 Leukemia Cells through Re-Expression of JAK/STAT Negative Regulators.

Asian Pac J Cancer Prev 2021 Mar 1;22(3):879-885. Epub 2021 Mar 1.

Centralized Laboratory Management Centre, Universiti Sultan Zainal Abidin, 22200 Besut, Terengganu, Malaysia.

Objective: The natural compound, thymoquinone (TQ) has demonstrated potential anticancer properties in inhibiting cell proliferation and promoting apoptosis in myeloid leukemia cells, breast cancer cells, and others. However, the effect mechanism of TQ on AML cells still not fully understood. In this study, the authors examined the effects of TQ on the expression of JAK/STAT-negative regulator genes SOCS-1, SOCS-3, and SHP-1, and their consequences on cell proliferation and apoptosis in HL60 leukemia cells.

Methods: MTT and trypan blue exclusion tests were conducted to determine the 50% inhibitory concentration (IC50) and cell proliferation. FITC Annexin and Guava® reagent were used to study the cell apoptosis and examine the cell cycle phases, respectively. The expression of JAK/STAT-negative regulator genes, SOCS-1, SOCS-3, and SHP-1, was investigated using reverse transcriptase- quantitative PCR (RT-qPCR).

Results: TQ demonstrated a potential inhibition of HL60 cell proliferation and a significant increase in apoptotic cells in dose and time-dependent manner. TQ significantly induced cycle arrest at G0-G1 phase (P < 0.001) and enhanced the re-expression of JAK/STAT-negative regulator genes.

Conclusion: TQ potentially inhibited HL60 cell proliferation and significantly increased apoptosis with re-expression of JAK/STAT-negative regulator genes suggesting that TQ could be a new therapeutic candidate for leukemia therapy.
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http://dx.doi.org/10.31557/APJCP.2021.22.3.879DOI Listing
March 2021

Antibacterial properties of selected Malaysian Tualang honey against and .

Iran J Microbiol 2020 Dec;12(6):565-576

Department of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Terengganu, Malaysia.

Background And Objectives: Tualang honey (TH) is a Malaysian multifloral jungle honey. In recent years, there has been a marked increase in the number of studies published in medical databases regarding its potential health benefits. The study aimed to investigate the effect of TH against and .

Materials And Methods: The effect of TH on both bacteria was investigated using MIC, MBC, growth curve, time-kill curve, scanning electron microscopy (SEM) and RT-qPCR.

Results: The MIC of TH against and was 18.5% (w/v) and 13% (w/v) respectively and MBC was 25% (w/v) for both bacteria. Spectrophotometric readings of at least 90% inhibition yielded MIC values of TH, 18.5% (w/v) and 15% (w/v) for and respectively. A time-kill curve demonstrated a bactericidal with a 4-log reduction estimated within 8 hours. Using SEM, loss of structural integrity and marked changes in cell shape were observed. RT-qPCR analysis showed that TH reduced the pattern of gene expression in both bacteria, with a trend toward reduced expression of the virulence genes of interest.

Conclusion: This study suggests that TH could potentially be used as an alternative therapeutic agent for microbial infection particularly against these two organisms.
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http://dx.doi.org/10.18502/ijm.v12i6.5031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884280PMC
December 2020

Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine.

Int J Hematol Oncol Stem Cell Res 2020 Jan;14(1):72-92

Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Acute myeloid leukemia (AML) is the most common form of acute leukemias in adults which is clinically and molecularly heterogeneous. Several risk and genetic factors have been widely investigated to characterize AML. However, the concomitant epigenetic factors in controlling the gene expression lead to AML transformation was not fully understood. This study was aimed to identify epigenetically regulated genes in AML cell lines induced by epigenetic modulating agents, Trichostatin A (TSA) and 5-Azacytidine (5-Aza). MV4-11 and Kasumi 1 were treated with TSA and/or 5-Aza at IC concentration. Gene expression profiling by microarray was utilized using SurePrint G3 Human Gene Expression v3. Gene ontology and KEGG pathway annotations were analyzed by DAVID bioinformatics software using EASE enrichment score. mRNA expression of the differentially expressed genes were verified by quantitative real time PCR. Gene expression analysis revealed a significant changes in the expression of 24,822, 15,720, 15,654 genes in MV4-11 and 12,598, 8828, 18,026 genes in Kasumi 1, in response to TSA, 5-Aza and combination treatments, respectively, compared to non-treated (<0.05). 7 genes (, , , , , and ) and 4 genes (, , and ) shown to be predominantly expressed in MV4-11 and Kasumi 1, respectively (EASE<0.1). The analysis also revealed phagosome pathway commonly activated in both cell lines. Our data showed a distinct optimal biological characteristic and pathway in different types of leukemic cell lines. These finding may help in the identification of cell-specific epigenetic biomarker in the pathogenesis of AML.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167603PMC
January 2020

Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with STAT3 Inactivation and Sensitivity Response to Imatinib in Resistant CML Cells

Asian Pac J Cancer Prev 2018 Jun 25;19(6):1585-1590. Epub 2018 Jun 25.

Diagnostic and Biomedicine, Faculty of Health Science, Universiti Sultan Zainal Abidin, Gong Badak Compus, Kuala Nerus, Terengganu, Malaysia. Email:

Background: Epigenetic silencing of tumor suppressor genes (TSG) is involved in development and progression of cancers. Re-expression of TSG is inversely proportionate with STAT3 signaling pathways. Demethylation of DNA by 5-Azacytidine (5-Aza) results in re-expression of silenced TSG. Forced expression of PRG2 by 5-Aza induced apoptosis in cancer cells. Imatinib is a tyrosine kinase inhibitor that potently inhibits BCR/ ABL tyrosine kinase resulting in hematological remission in CML patients. However, majority of CML patients treated with imatinib would develop resistance under prolonged therapy. Methods: CML cells resistant to imatinib were treated with 5-Aza and cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively. Gene expression analysis was detected by real time-PCR, STATs activity examined using Western blot and methylation status of PRG2 was determined by pyrosequencing analysis. Result: Expression of PRG2 was significantly higher in K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of PRG2 gene was significantly decreased in K562-R+5-Aza cells compared to other cells (p=0.021). STAT3 was inactivated in K562-R+5-Aza cells which showed higher sensitivity to imatinib. Conclusion: PRG2 gene is a TSG and its overexpression might induce sensitivity to imatinib. However, further studies are required to evaluate the negative regulations of PRG2 on STAT3 signaling.
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http://dx.doi.org/10.22034/APJCP.2018.19.6.1585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103584PMC
June 2018

Anti-Proliferative Effects of Dendrophthoe pentandra Methanol Extract on BCR/ABL-Positive and Imatinib-Resistant Leukemia Cell Lines

Asian Pac J Cancer Prev 2016 11 1;17(11):4857-4861. Epub 2016 Nov 1.

School of Health Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Malaysia.

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R (IC50= 192 μg/mL) compared to K562 (500 μg/ mL) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.
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http://dx.doi.org/10.22034/APJCP.2016.17.11.4857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454686PMC
November 2016

Enhancing SHP-1 expression with 5-azacytidine may inhibit STAT3 activation and confer sensitivity in lestaurtinib (CEP-701)-resistant FLT3-ITD positive acute myeloid leukemia.

BMC Cancer 2015 Nov 7;15:869. Epub 2015 Nov 7.

Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.

Background: Tumor-suppressor genes are inactivated by methylation in several cancers including acute myeloid leukemia (AML). Src homology-2 (SH2)-containing protein-tyrosine phosphatase 1 (SHP-1) is a negative regulator of the JAK/STAT pathway. Transcriptional silencing of SHP-1 plays a critical role in the development and progression of cancers through STAT3 activation. 5-Azacytidine (5-Aza) is a DNA methyltransferase inhibitor that causes DNA demethylation resulting in re-expression of silenced SHP-1. Lestaurtinib (CEP-701) is a multi-targeted tyrosine kinase inhibitor that potently inhibits FLT3 tyrosine kinase and induces hematological remission in AML patients harboring the internal tandem duplication of the FLT3 gene (FLT3-ITD). However, the majority of patients in clinical trials developed resistance to CEP-701. Therefore, the aim of this study, was to assess the effect of re-expression of SHP-1 on sensitivity to CEP-701 in resistant AML cells.

Methods: Resistant cells harboring the FLT3-ITD were developed by overexposure of MV4-11 to CEP-701, and the effects of 5-Aza treatment were investigated. Apoptosis and cytotoxicity of CEP-701 were determined using Annexin V and MTS assays, respectively. Gene expression was performed by quantitative real-time PCR. STATs activity was examined by western blotting and the methylation profile of SHP-1 was studied using MS-PCR and pyrosequencing analysis. Repeated-measures ANOVA and Kruskal-Wallis tests were used for statistical analysis.

Results: The cytotoxic dose of CEP-701 on resistant cells was significantly higher in comparison with parental and MV4-11R-cep + 5-Aza cells (p = 0.004). The resistant cells showed a significant higher viability and lower apoptosis compared with other cells (p < 0.001). Expression of SHP-1 was 7-fold higher in MV4-11R-cep + 5-Aza cells compared to parental and resistant cells (p = 0.011). STAT3 was activated in resistant cells. Methylation of SHP-1 was significantly decreased in MV4-11R-cep + 5-Aza cells (p = 0.002).

Conclusions: The restoration of SHP-1 expression induces sensitivity towards CEP-701 and could serve as a target in the treatment of AML. Our findings support the hypothesis that, the tumor-suppressor effect of SHP-1 is lost due to epigenetic silencing and its re-expression might play an important role in re-inducing sensitivity to TKIs. Thus, SHP-1 is a plausible candidate for a role in the development of CEP-701 resistance in FLT3-ITD+ AML patients.
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http://dx.doi.org/10.1186/s12885-015-1695-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637135PMC
November 2015

Apoptosis induction in MV4-11 and K562 human leukemic cells by Pereskia sacharosa (Cactaceae) leaf crude extract.

Asian Pac J Cancer Prev 2014 ;15(1):475-81

Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia E-mail :

Background: Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia.

Materials And Methods: Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. IC50 concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting.

Results: P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells.

Conclusions: These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.
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http://dx.doi.org/10.7314/apjcp.2014.15.1.475DOI Listing
November 2014

Association of ABO blood groups with diabetes mellitus.

Libyan J Med 2010 Feb 8;5. Epub 2010 Feb 8.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia.

Objective: So far no studies have been performed in Malaysia to look at association of diabetes mellitus (DM) with blood groups. We studied the association of ABO blood groups with DM type 2.

Patients And Methodology: It was a case control study conducted at Kepala Batas Hospital Batas, Penang, Malaysia in the year 2009, involving 70 patients with DM type 2 and 140 healthy controls. Ethical approval was obtained from Universiti Sains Malaysia. Blood samples were collected from the patients after consent. Samples were tested for ABO blood groups using ID-Card gel method.

Results: Chi-square test results showed that there was an association between the ABO blood groups and DM type 2. It was found that A and O blood groups were negatively associated with DM type 2 (P<0.05) with higher percentage of A and O groups individuals were non-diabetic. No significant association was noted between DM type 2 and blood groups B (P=0.423) and AB (P=0.095). It was also noted that B blood group was distributed with highest percentage among patients with DM type 2 (53.71%) compared to controls (22.52%), but no statistical significance achieved.

Conclusion: The results obtained suggest that there was a negative association between ABO blood groups A and O with DM type 2, with A and O group having less chances of diabetes. Large studies in other ethnic groups are needed to confirm these results.
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http://dx.doi.org/10.3402/ljm.v5i0.4847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071167PMC
February 2010