Pui-Kwong Chan, Ph.D.
Professor, Department of Pharmacology
Education and Awards
- Ph.D. University of Toronto (1978)
- Postdoctoral Training, Baylor College of Medicine, Houston, Texas
Anti-tumor Agents and Mechanism
The current research in this laboratory focus in the identification of new agents for cancer treatment and understanding of the drug mechanism.
- Identification and purification of Anti-tumor agents from Chinese medicine. Herbal Medicine has been a common therapeutic approach for various illnesses, including cancerous tumors, for centuries. Several putative anti-tumor plant-extracts from China are currently being examined. Xanthoceras sorbifolia Bunge (Sapindaceae) were used as folk medicine in inner Mongolia, China. We found that the extract from the husk of this plant has anti-tumor effect. The active compound was purified and its structure identified to be a novel triterpenoid saponin. It was named Xanifolia-Y. In vivo studies with Xanifolia-Y employing human ovarian carcinoma xenograft in mouse indicate that Xanifolia-Y is capable of extending the life span of animals bearing late stage tumors. Application of this drug and the structure/function relationship is the focus of current research. The goal of this project is to identify the cellular target site and to understand the drug mechanism.
- Effect of anticancer drugs on nucleolar protein Nucleophosmin/B23. The cell nucleus is the site where gene expression is executed and, as a result, dictates the fate of every cell. It is composed of complex substructures and contains multiple nucleoli where ribosome is synthesized. Many anticancer drugs target nucleoli and affect its function. NPM (Nucleophosmin/B23) is a major nucleolar protein that shuttles between nucleoli and cytoplasm. It involves multiple function in cells including ribosome assembly and transportation. Recently, it has been found that NPM plays a major role in centrosome replication, which couples to cell-cycle events. Many anticancer drugs cause dissociation of NPM from nucleoli to the nucleoplasm (NPM-translocation). Current studies include the drug-induced NPM-translocation mechanism and its relationship with apoptosis.
- Liu QR and Chan PK: (1993) Characterization of seven pseudogenes of nucleophosmin/B23 in the human genome. DNA and Cell Biology. 12: 149-156.
- Finch RA, Revankar GR and Chan PK: (1993) Nucleolar localization of nucleophosmin/B23 requires GTP. J. Biol. Chem. 268: 5823-5827.
- Valdez BC, Perlaky L, Henning D, Saijo Y, Chan PK and Busch H: (1994) Identification of the nuclear and nucleolar localization signals of the protein p120 . Interaction with translocation protein B23. J. Biol. Chem. 269: 23776-23783.
- Chan PK and Chan FY: (1995) Nucleophosmin/B23 (NPM) oligomer is a major and stable entity in HeLa cells. Biochim. Biophys. Acta. 1262: 37-42.
- Finch RA, Chang D and Chan PK: (1995) GTP S restores nucleophosmin (NPM) localization to nucleoli of GTP-depleted HeLa cells. Molecular and Cellular Biochemistry. 146: 171-178.
- Chan PK, Qi Y, Amley J and Koller CA: (1996) Quantitation of the NPM-translocation using imaging analysis. Cancer Letter. 100: 191-197.
- Finch RA and Chan PK: (1996) ATP depletion affects NPM translocation and exportation of rRNA from nuclei. Biochem. Biophys. Res. Commun. 222: 553-558.
- Chan PK, Chan FY, Morris SW and Xie Z: (1997) Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5í enhancer region. Nucleic Acid Research. 25: 1225-1232.
- Finch RA, Revanka GA and Chan PK: (1997) Structural and functional relationships of toyocamycin on NPM-translocation. Anti-Cancer Drug Design. 12: 205-215.
- Chan PK and Chan, FY: (1999) A study of correlation between NPM-translocation and apoptosis in cells induced by daunomycin. Biochemical Pharmacology. 57: 1265-1273.
- Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE and Fukasawa K: (2000) Nucleophomin/B23 is a target of CDK2/Cyclin E in centrosome duplication. Cell. 103: 127-140.
- Chan PK: (2003) Inhibition of tumor growth in vitro by the extract of fagopyrum cymosum (fago-c). Life Sciences. 72: 1851-1858.
- Chan PK: (2007) Acylation with diangeloyl groups at C21-22 position in triterpenoid saponins is essential for cytotoxicity towards tumor cells. Biochem. Pharmacology 73: 341-350.
- Chan PK, Zhao M, Che CT and Mak E: (2008) Cytotoxic acylated triterpene saponins from the husks of Xantoceras sorbifolia. J. Nat. Prod. 71:1247-1250.