Principal Investigators: Dr. Tang Cheuk On, Johnny

The main emphasis of my research team mainly involves three areas. The first aspect is about exploring the use of natural plant or animal products as novel anti-cancer agents and to understand the underlying molecular mechanisms of their anti-cancer actions. The second part mainly concerns with the chemical modifications of the identified active ingredients from the natural products with prominent anti-cancer effects for the purpose of novel drug discovery. The other research interest is to study the molecular mechanisms of pathogenesis in human esophageal squamous cell carcinoma (ESCC) and to identify the novel molecular targets for the future targeted therapy on ESCC and other cancers.

Exploring Natural Products as Anti-cancer Agents

Studied examples include the investigation on the anti-cancer effects of the extracts of Gleditsia sinensis, Ganoderma lucidum, Brucea javanica, Scutellaria barbata, Radix Sophorae tonkinensis and Mylabris phalerata. The molecular targets include the suppression of cyclooxygenase-2 and oncogenes expression, inhibition of telomerase activity and inducing apoptosis in cancer cells.

Discovery of Novel Small-Molecule Anti-cancer Drugs

Cantharidin derived from Mylabris phalerata extract was further chemically modified to produce the derivatives which are less toxic and more potent to be used as novel anti-cancer agents. The molecular targets of the anti-cancer include decreased G1 phase cell population, mitochondrial membrane potential collapse, caspase 3 activation and hence DNA fragmentation.

Molecular Pathogenesis of Esophageal Carcinoma

Esophageal cancer ranks the ninth most common malignancy and the sixth most frequent cancer death throughout the world, with special geographic variations in its incidence and histological subtypes. In China, esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of the total incidence of esophageal cancer, and it has been estimated that approximately 300,000 new cases of esophageal cancer are diagnosed every year in the world and nearly half of these cases originate in the high-incidence regions of China. In Hong Kong, ESCC ranks the sixth most frequent cancer death among all other cancers in male, which makes this tumor type of local importance for investigation.

My research group recently identified the novel oncogenes in ESCC (e.g. GAEC1, JK-1 and JS-1) and the normal cells can be transformed into tumor cells when the target oncogenes are overxpressed. The identified genes were also investigated as the novel targets for anti-cancer agents.

Related Publications:

1. Kok SHL, Chui CH, Lam WS, Chen J, Lau FY, Wong RSM, Cheng GYM, Lai PPS, Leung TWT, Yu MWY, Tang JCO*, Chan ASC. Synthesis and structure evaluation of a novel cantharimide and its cytotoxicity on SK-Hep1 hepatoma cells. Bioorganic & Medicinal Chemistry Letters, 17(5), 1155-1159 (2007).
2. Tang WK, Chui CH, Fatima S, Kok SHL, Pak KC, Ou TM, Hui KS, Wong MM, Wong J, Law S, Tsao SW, Lam KY, Beh PHL, Srivastava G, Ho KP, Chan ASC, Tang JCO*. Inhibitory effects of Gleditsia sinensis fruit extract on telomerase activity and oncogenic expression in human esophageal squamous cell carcinoma. International Journal of Molecular Medicine, 19(6):953-960 (2007)
3. Law FBF, Chen YW, Wong KY, Ying J, Tao Q, Langford C, Lee PY, Law S, Cheung RWL, Chui CH, Tsao GSW, Lam KY, Wong J, Srivastava G, Tang JCO*. Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma. Oncogene, 26(40):5877-5888 (2007)
4. Kok SHL, Gambari R, Chui CH, Yuen MCW, Lin E, Wong RSM, Lau FY, Cheng GYM, Lam WS, Chan SH, Lam KH, Cheng CH, Lai PBS, Yu MWY, Cheung F, Tang JCO*, Chan ASC. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines. Bioorganic & Medicinal Chemistry 16(7):3626-3631 (2008)
5. Kok SHL, Gambari R, Chui CH, Yuen MCW, Lin E, Wong RSM, Lau FY, Cheng GYM, Lam WS, Chan SH, Lam KH, Cheng CH, Lai PBS, Yu MWY, Cheung F, Tang JCO*, Chan ASC*. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines. Bioorganic & Medicinal Chemistry 16(7):3626-3631 (2008)
6. Chan SH, Lam KH, Chui CH, Gambari R, Yuen MCW, Wong RSM, Cheng GYM, Lau FY, Au YK, Cheng CH, Kok SHL, Tang JCO*, Chan ASC*. The preparation and in vitro antiproliferative activity of phthalimide based ketones on MDAMB-231 and SKHep-1 human carcinoma cell lines. European Journal of Medicinal Chemistry 44(6):2736-2740 (2009)