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Fulltext Matrix Metallopeptidase 3 Polymorphisms: Emerging genetic Markers in Human Breast Cancer Metastasis

Suhaimi SA, Chan SC, Rosli R

J Breast Cancer, 2020 Feb;23(1):1-9.
PMID: 32140265 DOI: 10.4048/jbc.2020.23.e17

Matrix metallopeptidase 3 or MMP3, is a zinc-dependent proteolytic enzyme that is involved in various physiological processes via modification of the extracellular matrix. In particular, its over-expression has been associated with cancer metastasis and tumor growth in various cancers including breast cancer. MMP3 gene expression is regulated by several factors such as DNA polymorphisms which also serve as risk factors for breast cancer. As such, DNA polymorphisms of MMP3 have the potential to be utilized as genetic biomarkers for prediction and prognosis of metastatic breast cancer. Presently, genome-wide association studies of MMP3 gene polymorphisms which are associated with breast cancer risk and patient survival in a variety of populations are reviewed. In order to understand the potential role of MMP3 polymorphisms as genetic markers for breast cancer metastasis, the domain structure of MMP3, the regulation of its expression and its role in breast cancer metastasis are also briefly discussed in this review. The emergence of MMP3 gene polymorphisms as prognostic biomarker candidates for breast cancer metastasis may contribute towards improving targeted therapies and categorization of breast cancer cases in order to provide a better and more accurate prognosis.
Occupational sitting time, its determinants and intervention strategies in Malaysian office workers: a mixed-methods study

Suhaimi SA, Müller AM, Hafiz E, Khoo S

Health Promot Int, 2021 Sep 13.
PMID: 34516620 DOI: 10.1093/heapro/daab149

Adults who accumulate a lot of sedentary time per day are at an increased risk of metabolic syndrome, type 2 diabetes, and hypertension. Prolonged sitting is also associated with depression, anxiety, bipolar disorder and schizophrenia. With the increase in desk-based office work, many office workers spend long hours sitting at the workplace. The aim of this study was to assess occupational sitting time in Malaysian government office workers, and investigate determinants of occupational sitting time and potential strategies to interrupt sitting time. We conducted a mixed-methods study consisting of a survey and focus group discussions (FGDs). A total of 1338 office workers from 24 Malaysian ministries completed the Occupational Sitting and Physical Activity Questionnaire. Twenty-nine office workers who spent at least 7 h per day sitting at work participated in FGDs. We enquired about knowledge, awareness and perceptions related to prolonged sitting time, barriers and facilitators to sitting time at work, and potential intervention strategies. Mean daily sitting time at work was 5.96 h (standard deviation = 1.37 h). FDGs confirmed barriers and facilitators to sitting time in accordance with the social-ecological model for health. Intrapersonal, social and physical environmental factors as well as organizational culture and organizational policy were mentioned to affect occupational sitting time. The results show that Malaysian government office workers spent a significant amount of time sitting at work and we identified multi-level factors influencing sitting time. A smartphone-based intervention to interrupt sitting time at work was suggested and is currently being tested.
Rutamarin, an Active Constituent from Ruta angustifolia Pers., Induced Apoptotic Cell Death in the HT29 Colon Adenocarcinoma Cell Line

Suhaimi SA, Hong SL, Abdul Malek SN

Pharmacogn Mag, 2017 Jul;13(Suppl 2):S179-S188.
PMID: 28808378 DOI: 10.4103/pm.pm_432_16

BACKGROUND: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine.
OBJECTIVE: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death.
MATERIALS AND METHODS: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers. were initially investigated for their cytotoxic activity against two human carcinoma cell lines (MCF7 and HT29) and a normal human colon fibroblast cell line (CCD-18Co) using sulforhodamine B cytotoxicity assay. Eight compounds including rutamarin were isolated from the active chloroform extract and evaluated for their cytotoxic activity against HT29 human colon carcinoma cell line and CCD-18Co noncancer cells. Further studies on the induction of apoptosis such as morphological examinations, biochemical analyses, cell cycle analysis, and caspase activation assay were conducted in rutamarin-treated HT29 cells.
RESULTS: Rutamarin exhibited remarkable cytotoxic activity against HT29 cells (IC50 value of 5.6 μM) but was not toxic to CCD-18Co cells. The morphological and biochemical hallmarks of apoptosis including activation of caspases 3, 8, and 9 were observed in rutamarin-treated HT29 cells. These may be associated with cell cycle arrest at the G0/G1 and G2/M checkpoints, which was also observed in HT29 cells.
CONCLUSIONS: The present study describes rutamarin-induced apoptosis in the HT29 cell line for the first time and suggests that rutamarin has the potential to be developed as an anticancer agent.
SUMMARY: Rutamarin was cytotoxic to HT29 colon cancer cells but exerted no damage to normal colon cellsRutamarin induced morphological and biochemical hallmarks of apoptosis in HT29 cellsRutamarin induced cell cycle arrest at the G0/G1 and G2/M checkpoints in a dose-dependent manner in HT29 cellsRutamarin activated caspases 3, 8, and 9 in a dose-dependent manner in HT29 cells. Abbreviations used: ACN: Acetonitrile, ANOVA: One-way analysis of variance, BrdU: Bromodeoxyuridine, 13C-NMR: Carbon-13 Nuclear magnetic resonance, CAD: Caspase-activated endonuclease, CCD-18Co: Human colon normal, DLD1: Human Duke's type C colorectal adenocarcinoma, DMRT: Duncan's multiple range test, DMSO: Dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DR4/5: Death receptor 4/5 protein, EMEM: Eagle's minimum essential media, FBS: Fetal bovine serum, FITC Annexin V: Annexin V conjugated with fluorescein isothiocyanate, FITC-DEVD-FMK: Fluorescein isothiocyanate conjugate of caspase inhibitor Asp-Glu-Val-Asp-fluoromethyl ketone, FITC-IETD-FMK: Fluorescein isothiocyanate conjugate of caspase inhibitor Ile-Glu-Thr-Asp-fluoromethyl ketone, FITC-LEHD-FMK: Fluorescein isothiocyanate conjugate of caspase inhibitor Leu-Glu-His-Asp-fluoromethyl ketone, G0: Quiescent phase of cell cycle, G1: Gap 1 phase of cell cycle, G2: Gap 2 phase of cell cycle, GC-MS: Gas chromatography-mass spectrometry, HeLa: Human cervical adenocarcinoma, HPLC: High performance liquid chromatography, HT29: Human colon adenocarcinoma, Huh7.5: Human hepatocellular carcinoma, IC50: Half maximal inhibitory concentration, KSHV: Kaposi's sarcoma-associated herpesvirus, M phase: Mitotic phase of cell cycle, MCF7: Human breast adenocarcinoma, NMR: Nuclear magnetic resonance, PBS: Phosphate-buffered saline, PI: Propidium iodide, RNase: Ribonuclease, rt: Retention time, S phase: Synthesis phase of cell cycle, SD: Standard deviation, SRB: Sulforhodamine B, TCA: Trichloroacetic acid, TLC: Thin layer chromatography, TNF-R1: Tumor necrosis factor receptor 1 protein, TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling, UV: Ultraviolet.
Purification, biochemical characterisation and bioinformatic analysis of recombinant farnesol dehydrogenase from Theobroma cacao

Satyaveanthan MV, Suhaimi SA, Ng CL, Muhd-Noor ND, Awang A, Lam KW, et al.

Plant Physiol Biochem, 2021 Apr;161:143-155.
PMID: 33588320 DOI: 10.1016/j.plaphy.2021.01.050

The juvenile hormones (JH) in plants are suggested to act as a form of plant defensive strategy especially against insect herbivory. The oxidation of farnesol to farnesoic acid is a key step in the juvenile hormone biosynthesis pathway. We herein present the purification and characterisation of the recombinant Theobroma cacao farnesol dehydrogenase enzyme that catalyses oxidation of farnesol to farnesal. The recombinant enzyme was purified to apparent homogeneity by affinity chromatography. The purified enzyme was characterised in terms of its deduced amino acid sequences, phylogeny, substrate specificity, kinetic parameters, structural modeling, and docking simulation. The phylogenetic analysis indicated that the T. cacao farnesol dehydrogenase (TcFolDH) showed a close relationship with A. thaliana farnesol dehydrogenase gene. The TcFolDH monomer had a large N-terminal domain which adopted a typical Rossmann-fold, harboring the GxxGxG motif (NADP(H)-binding domain) and a small C-terminal domain. The enzyme was a homotrimer comprised of subunits with molecular masses of 36 kDa. The TcFolDH was highly specific to NADP+ as coenzyme. The substrate specificity studies showed trans, trans-farnesol was the most preferred substrate for the TcFolDH, suggesting that the purified enzyme was a NADP+-dependent farnesol dehydrogenase. The docking of trans, trans-farnesol and NADP+ into the active site of the enzyme showed the important residues, and their interactions involved in the substrate and coenzyme binding of TcFolDH. Considering the extensive involvement of JH in both insects and plants, an in-depth knowledge on the recombinant production of intermediate enzymes of the JH biosynthesis pathway could help provide a potential method for insect control.
Fulltext Physical Activity Promotion in Malaysia: Challenges and Opportunities

Khoo S, Poh BK, Suhaimi SA, Chong KH, Ramirez Varela A

Front Public Health, 2020;8:536239.
PMID: 33194945 DOI: 10.3389/fpubh.2020.536239

About three quarters of the Malaysian adult population are physically active. There has been growth in physical activity and health research since 2010, with most studies being observational in design and few included objective measures of physical activity. The Malaysian Ministry of Health has published physical activity guidelines, strategies and action plans aimed at promoting physical activity. Physical activity promotion activities have included national campaigns and programmes which target different populations. Further work that incorporates the WHO Global Action Plans on Physical Activity (GAPPA), as well as a more systemic approach is needed, to promote physical activity and a healthy lifestyle. High-level multi-stakeholder collaboration is required for continuing expansion and strengthening of research capacity, and for bridging the physical activity policy gaps in Malaysia.
Molecular characterization and enzyme inhibition studies of NADP+- farnesol dehydrogenase from diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae)

Zifruddin AN, Mohamad-Khalid KA, Suhaimi SA, Mohamed-Hussein ZA, Hassan M

Biosci Biotechnol Biochem, 2021 Jun 24;85(7):1628-1638.
PMID: 33890631 DOI: 10.1093/bbb/zbab072

Juvenile hormone III (JH III) plays an important role in insect reproduction, development, and behavior. The second branch of JH III production includes oxidation of farnesol to farnesal by farnesol dehydrogenase. This study reported the identification and characterization of Plutella xylostella farnesol dehydrogenase (PxFoLDH). Our results showed that PxFoLDH belongs to the short-chain dehydrogenase/reductase superfamily, consisting of a single domain with a structurally conserved Rossman fold, an NAD(P) (H)-binding region and a structurally diverse C-terminal region. The purified enzyme displayed maximum activity at 55$\ $°C with pH 9.5 and was stable in the temperature below 70$\ ^\circ $C. PxFoLDH was determined to be a monomer with a relative molecular weight of 27 kDa and highly specific for trans, trans-farnesol, and NADP+. Among analog inhibitors tested, farnesyl acetate was the most effective inhibitor with the lowest Ki value of 0.02 µm. Our findings showed this purified enzyme may represent as NADP+-farnesol dehydrogenase.