Manumycin A의 Caspase 활성으로 인한 SGT 세포주에서 아팝토시스 유도효과 Manumycin A Induced Apoptotic Effect on SGT Cell Line by Caspase Activation
pp.327-336
AJthough salivary gland adenocarcinoma accounts for third prevalence rate of all salivary gland tumors. it is one of the most aggressive solid tumors. Current therapy does not s ignificantly improve survival rates. Thus‘ investigating new therape utic modali t ies aga inst sali va ry gland adenocarcinoma is necessary. Manumycin A. a natural product o{ Streptα7Jyces parvuJus‘ inhi bits farn esy l- transferase by competition with farnesyl pyrophosphate groups . Manumycin has shown antitumor activity in several ex per‘ imental systems through identifying the regulatory pathway of apoptosis. The hi erarchical relationship of caspase-8 to caspase-3 and caspase-9 in the drug-induced a poptosis pathway in antitumol effect is not clear. The hi erarchical relations hip between cytochrome c and the caspases and provided evidence to support the hypothesis that the release of cytochrome c was upstream of caspase activation in the enhanced apoptosis induced by manumycin A Manumycin A has not been examined extensively in human salivary gland tumor and has not yet been clarified. The purpose of this study were to investigate mRNA and protein expression of Bc l- 2 、Bax, Cytochrome C‘ caspase- 3 , 一8 and -9 in SGT cell line by RT-PCR and immunoslot blotting, and to a pply its results to exami ne iLs chemoprevention for salivary gland adenocarcinoma. MTI assay showed about 50% cellular viability of SGT cell line treated by 50μM manunycin A Bcl-2. Bax‘ and caspase-8 mRNA expression in SGT cell line were unchangeable after 50μM manu nycin A Cytochrome C‘ caspase-3 and -9 showed about 1.5-5 folds higher mRNA expression in SGT cell line than that of control a nd DMSO- t reated group a fter 50M manunycin A. Bcl-2, Bax, and caspase-8 protein expression in SGT ce ll line were unchangcable after 50μM manunycin A. Cy Lochrorne C, caspase-3 and -9 showed about 2-7 fo lds higher protein express ion in SGT cell line than that of control and DMSO-treated group after 50μM manunycin A. mRNA expression was assoc iated with protein expression in SGT cell line after 50μM manunycin A. It suggested that manumycin A would induce poptotic effect on SGT cell line by caspase-3 and - 9 activation through cytochrorne c release. And man umycin A will be a useful chemoprevention drug for human salivary gland carcinoma in future.