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Christia vespertilionis extract induced antiproliferation and apoptosis in breast cancer (MCF7) cells

Ismail NZ, Adebayo IA, Mohamed WAS, Mohamad Zain NN, Arsad H

Mol Biol Rep, 2021 Nov;48(11):7361-7370.
PMID: 34665399 DOI: 10.1007/s11033-021-06743-w

BACKGROUND: C. vespertiliomis extracts were evaluated for antiproliferative and apoptosis effect on breast cancer (MCF7) cells.
METHODS AND RESULTS: The leaves extracts were analysed for its antiproliferative effect on breast cancer (MCF7) cells and normal epithelial breast (MCF 10A) cells using Sulforhodamine B (SRB) assay. The selective extract was evaluated for its ability to induce apoptosis using Annexin V-FITC apoptosis staining and the expression of molecular genes using qualitative reverse transcription-polymerase chain reaction (RT-PCR) against MCF7 cells. Gas chromatography-mass spectrometry (GC-MS) was used to identify the compounds from the selective extract. The findings showed that dichloromethane fraction (CV-Dcm) extract had high antiproliferative effect against MCF7 cells (IC50 = 24 µg/mL, selective index (SI) = 8.17). The percentages of apoptosis cells in CV-Dcm-treated MCF7 cells was 58.8%. The CV-Dcm extract induced downregulation of PCNA level. The apoptotic genes were also triggered in both extrinsic and intrinsic signaling pathways, affecting a 1.5-fold increase in BAX, 1.4-fold increase in cytochrome c, 1.3-fold increase in caspase-8, 1.7-fold increase in caspase-3 and 0.5-fold-decrease in BCL-2. Treated MCF7 cells also activated P53-dependent apoptotic death pathway.
CONCLUSIONS: The present work strongly suggests that high efficacy of CV-Dcm extract was attributed to its antiproliferative and apoptosis-inducing activation in MCF7 cells, most likely due to its favourable compounds.
Pharmacological advances in anti-retroviral therapy for human immunodeficiency virus-1 infection: A comprehensive review

Azzman N, Gill MSA, Hassan SS, Christ F, Debyser Z, Mohamed WAS, et al.

Rev Med Virol, 2024 Mar;34(2):e2529.
PMID: 38520650 DOI: 10.1002/rmv.2529

The discovery of anti-retroviral (ARV) drugs over the past 36 years has introduced various classes, including nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitor, fusion, and integrase strand transfer inhibitors inhibitors. The introduction of combined highly active anti-retroviral therapies in 1996 was later proven to combat further ARV drug resistance along with enhancing human immunodeficiency virus (HIV) suppression. As though the development of ARV therapies was continuously expanding, the variation of action caused by ARV drugs, along with its current updates, was not comprehensively discussed, particularly for HIV-1 infection. Thus, a range of HIV-1 ARV medications is covered in this review, including new developments in ARV therapy based on the drug's mechanism of action, the challenges related to HIV-1, and the need for combination therapy. Optimistically, this article will consolidate the overall updates of HIV-1 ARV treatments and conclude the significance of HIV-1-related pharmacotherapy research to combat the global threat of HIV infection.
Fulltext GC-MS Evaluation, Antioxidant Content, and Cytotoxic Activity of Propolis Extract from Peninsular Malaysian Stingless Bees, Tetrigona Apicalis

Mohamed WAS, Ismail NZ, Omar EA, Abdul Samad N, Adam SK, Mohamad S

Evid Based Complement Alternat Med, 2020;2020:8895262.
PMID: 33381215 DOI: 10.1155/2020/8895262

INTRODUCTION: Propolis has been used traditionally in several countries for treating various diseases as it possessed healing properties including antioxidant and anticancer qualities. In Peninsular Malaysia, Tetrigona apicalis is one of the species of stingless bees mainly found in virgin jungle reserves which largely contribute to propolis production. Therefore, this study is designed to evaluate the phytochemical contents, antioxidant properties, and the cytotoxic effect of ethanolic crude of propolis extract against MCF7 and MCF 10A cell lines.
METHOD: The ethanolic extract of propolis (EEP) was extracted using 80% ethanol. Identification of phytochemical contents and antioxidant properties of EEP was analysed by gas chromatography-mass spectrometry (GC-MS) and using 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) method, respectively. The EEP cytotoxic activity was evaluated on MCF7 and MCF 10A using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.
RESULTS: Phytochemical contents of EEP demonstrated 28 compounds in which caryophyllene (99%), β-amyrin (96%), α-amyrin (93%), and caryophyllene oxide (93%) were the main compounds. The percentage of ABTS+ scavenging activity of EEP showed an inhibition of 9.5% with half-inhibitory concentration (IC50) value of 1.68 mg/mL. The EEP reduced MCF7 cells viability at IC50 value of 62.24 μg/mL, 44.15 μg/mL, and 32.70 μg/mL at 24, 48, and 72 hours, respectively. The IC50 value of MCF 10A was 49.55 μg/mL, 56.05 μg/mL, and 72.10 μg/mL at 24, 48, and 72 hours, respectively. The EEP cytotoxic effect of T. apicalis was more selective towards MCF7 at 72-hour incubation with a selectivity index (SI) of 2.20.
CONCLUSION: The EEP has been shown to have antioxidants and potential bioactive compounds and inhibited proliferation of the MCF7 cells. Further studies on the EEP role in the apoptosis pathway and its screening towards other cell lines will be evaluated.
Molecular docking and molecular dynamic simulations of apoptosis proteins with potential anticancer compounds present in Clinacanthus nutans extract using gas chromatography-mass spectrometry

Ismail NZ, Mohamed WAS, Ab Rahim N, Hashim NM, Adebayo IA, Mohamad Zain NN, et al.

J Biomol Struct Dyn, 2023;41(13):6104-6120.
PMID: 35899385 DOI: 10.1080/07391102.2022.2101530

Clinacanthus nutans is a medicinal plant recognised for its anticancer properties. We previously discovered that the C. nutans extract had the most potent inhibitory effect on MCF7 breast cancer cell and significantly induced apoptosis. However, there is a scarcity of studies demonstrating the molecular interactions of C. nutans-derived chemical compounds associated with apoptosis-related proteins. Therefore, the objective of this study was to determine the potential chemical compounds found in the C. nutans extract and examine their interactions with the targeted apoptotic proteins using molecular docking and molecular dynamic simulations. To address this objective, the compounds found in the SF2 extract of C. nutans were analysed using Gas Chromatography-Mass Spectrometry (GC-MS). The molecular interaction of the compounds with the targeted apoptotic proteins were determined using molecular docking and molecular dynamic simulations. GC-MS analysis revealed a total of 32 compounds in the SF2 extract. Molecular docking analysis showed that compound β-amyrenol had the highest binding affinity for MDM2-P53 (-7.26 kcal/mol), BCL2 (-11.14 kcal/mol), MCL1-BAX (-6.42 kcal/mol), MCL1-BID (-6.91 kcal/mol), and caspase-9 (-12.54 kcal/mol), whereas campesterol had the highest binding affinity for caspase-8 (-10.11 kcal/mol) and caspase-3 (-10.14 kcal/mol). These selected compounds were subjected to molecular dynamic simulation at 310 K for 100 ns. The results showed that the selected protein-ligand conformation complexes were stable, compact, and did not alter much when compared to the protein references. The findings indicate that β-amyrenol and campesterol are potentially significant compounds that might provide insight into the molecular interactions of the compounds with the apoptosis-related proteins.Communicated by Ramaswamy H. Sarma.
Fulltext Ethnic disparities and its association between epicardial adipose tissue thickness and cardiometabolic parameters

Mohamed W, Ishak KN, Baharum N, Zainudin N, Lim HY, Noh M, et al.

Adipocyte, 2024 Dec;13(1):2314032.
PMID: 38373876 DOI: 10.1080/21623945.2024.2314032

Excessive deposit of epicardial adipose tissue (EAT) were recently shown to be positively correlated with cardiovascular disease (CVD). This study aims to investigate the thickness of EAT and its association with the components of metabolic syndrome among multi-ethnic Malaysians with and without acute coronary syndrome (ACS). A total of 213 patients were recruited, with the thickness of EAT were quantified non-invasively using standard two-dimensional echocardiography. EAT thickness among the Malaysian population was prompted by several demographic factors and medical comorbidities, particularly T2DM and dyslipidaemia. ACS patients have significantly thicker EAT compared to those without ACS (4.1 mm vs 3.7 mm, p = 0.035). Interestingly, among all the races, Chinese had the thickest EAT distribution (4.6 mm vs 3.8 mm), with age (p = 0.04 vs p