PROF. DR. TENGKU SIFZIZUL BIN TENGKU MUHAMMAD

tel       : +609-6683103

fax      : +609-6683105

Guat-Siew Chew, Stephen Myers, Alexander Chong Shu-Chien, Tengku Sifzizul Tengku Muhammad (2014) Interleukin-6 inhibition of peroxisome proliferator-activated receptor alpha expression is mediated by JAK2- and PI3K-induced STAT1/3 in HepG2 hepatocyte cells. Mol. Cell. Biochem. 388, 25-37

Kheng Leong Ooi, Tengku Sifzizul Tengku Muhammad, Lee Yein Lam and Shaida Fariza Sulaiman (2014) Cytotoxic and Apoptotic    Effects of Ethyl Acetate Extract of Elephantopus mollis Kunth. in Human Liver Carcinoma HepG2 Cells Through Caspase-3 Activation. Integr. Cancer. Ther. 13, NP1-NP9

Kheng Leong Ooi, Tengku Sifzizul Tengku Muhammad, Shaida Fariza Sulaiman (2013) Physalin F from Physalis minima L. triggers apoptosis-based cytotoxic mechanism in        T-47D cells through the activation caspase-3 and c-myc-dependent pathways. J.Ethnopharm. 150, 382-388

Guat-Siew Chew, Stephen Myers, Kheng Leong Ooi, Alexander Chong Shu-Chien, Tengku Sifzizul Tengku Muhammad (2013) Interleukin-6 Induces the Down Regulation of Human Peroxisome Proliferator Activated  Receptor Alpha via the MAPK-induced STAT Pathway in Human Hepatocytes. J Biochem. Pharmacol. Res. 1, 204-211

Lim, W.S., Ng, D.L., Kor, S.B., Wong, H.K., Tengku-Muhammad, T.S., Choo, Q.C., Chew, C.H. (2013) Tumour necrosis factor alpha down-regulates the expression of peroxisome proliferator activated receptor alpha (PPARα) in human hepatocarcinoma HepG2 cells by activation of NF-κB pathway. Cytokine 61, 266-274

RESEARCH SUMMARY

Elucidation of the role of peroxisome proliferator activated receptor alpha (PPARα) in acute phase response

The acute phase response is an orchestrated response to tissue    injury, infection or inflammation. A prominent feature of this     response is the induction of a number of plasma  proteins,            collectively known as acute phase proteins by liver cells in response to cytokines produced by macrophages. PPARα is a member of the PPAR subfamily of nuclear hormone receptors that regulates gene expression    following dimerization with retinoic X receptor (RXR)         subfamily by binding to specific sequences localised in the promoter region of target genes. PPARα is highly expressed in liver and has been implicated in the regulation of genes involved in lipid         metabolism, atherosclerosis and inflammation. Therefore, our interests are to dissect the signal transduction pathways which are     responsible in regulating the expression of PPARα and to elucidate the molecular mechanisms taken by PPAR in modulating the      expression of the genes encoding acute-phase proteins during           acute-phase response.

Identification of small molecules as therapeutic agents for atherosclerosis and diabetes using target-based high-throughput screening platforms

Cardiovascular disease (CVD) such as heart attacks still   remains the leading cause of death worldwide. The underlying cause of CVD is atherosclerosis. One of the major risk factors of atherosclerosis is hypercholesterolaemia. High-density   lipoprotein (HDL) is an important molecule that involves in     reverse cholesterol transport by delivering the cholesterol to the liver via a receptor present on the surface of liver cells known as Scavenger Receptor-Type B1 (SR-B1), a PPAR target gene. Our lab has successfully developed a             high-throughput platform utilisng SR-B1 as the target for the screening of small molecules (natural and synthetic          compounds) with a potent activity in reducing blood           cholesterol levels.

Diabetes mellitus is a leading metabolic disorder that leads to high blood glucose levels due to resistance or insufficient   production of insulin. It was widely reported that the incidence of atherosclerosis is accelerated in patients with type II       diabetes. Curently, one of the widely use drugs for type 2 diabetes is Thiazolidinediones (TZD). These molecules act by binding and activating PPARg as its ligands. Our lab has  established a cell-based high throughput screening platform by utilizing a chimaeric plasmid harbouring PPARg binding sites (peroxisome proliferator responsive elements, PPRE) linked to a reporter system, luciferase. Small molecules     provided by our collaborators will be subjected to the         developed screening platform to identifiy the compounds with potent activity as PPARg ligand.

In addition, our lab is also involved in the identification of small molecules that exhibit the cytotoxicity activity in breast, cervical and liver cancer cells.

The mechanisms of action of the potent molecules in the regulating the cellular and molecular events in atherosclerosis, diabetes and cancer are also elucidated.

1. Eskitis Institute for Drug Discovery, Griffith University
2. Universiti Sains Malaysia
3. Universiti Malaysia Sabah
4. Malaysian Institute of Pharmaceuticals and         Nutraceuticals

Ooi KL, Tengku Muhammad TS, Sulaiman SF (2010) Growth arrest and induction of apoptotic and non-apoptotic programmed cell death by, Physalis minima L. chloroform extract in human ovarian carcinoma Caov-3 cells. J. Ethnopharm. 128, 92-99

Choy-Hoong Chew, Guat-Siew Chew, Nazalan Najimudin and Tengku Sifzizul Tengku-Muhammad (2007) Interleukin-6 inhibits human peroxisome proliferator activated receptor alpha gene expression via CCAAT/enhancer-binding proteins in hepatocytes. Int. J. Biochem. Cell Biol. 39, 1975-1986