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Curcurmin induce apoptosis in human cervix epithelioid carcinoma cells (HeLa) through activation of caspase- 3 and P53  C-S Yu PhDa, JK-S Chan Bsb, J-G Chung PhDc

a, Center of General Education, cDepartment of Microbiology; China Medical University, Taichung 404, Taiwan, bDepartment of Biochemistry, University of British Columbia, Vancouver, BC, Canada

Curcurmin has been demonstrated in rats to prevent azoxymethane-induced aberrant crypt foci, putative precursor lesions in the colon and in mice to prevent tumorigenesis induced by azoxymethane in the colon and by N-ethyl N-nitrosoguanidine in the duodenum and forestomach. The mechanism of curcurmin affect on human cervix cancer cells was not addressed. Therefore, curcurmin was used to study the biological activities on the human cervix epithelioid carcinoma cells (HeLa). On MTT assay, curcurmin showed obvious cytotoxic effects and inhibit the proliferation of HeLA cells. The cytotoxic effects of curcurmin was accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including DNA fragmentation (gel electrophoresis) and sub-G1 ratio (flow cytometric assay). The HeLA cells cotreated with curcurmin caused a rapid transient induction of caspase-3 activity, but not caspase-1 activity. We also found out that cleavage of poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase-3 protein were detected in curcurmin-treated HeLa cells. Increased the pro-apoptotic protein (bax), cytochrome C release and caspases-9 and 3 activity and decreased anti-apoptotic protein (Mcl-1) were detected in HeLa cells after cotreated with curcurmin. We also used PCR and multiplex PCR methods to examine the caspase 3 gene expression and the results show that curcurmin induced caspase-3 gene expression.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 795 (Apoptosis mechanisms).




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