Ethyl 2- [N-p-chlorobenzyl- (2'-methyl) ] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01007) induces apoptosis in human cervical cancer Ca Ski cells
Lin, T-Ping.; Huang, A-Cheng.; Wei, H-Chuan.; Lin, J-Gung.; Chung, J-Gung.
In Vivo 21(2): 397-406
2007
ISSN/ISBN: 0258-851X PMID: 17436594 Document Number: 614329
The cytotoxic effects of a new compound, ethyl 2[N-p-chloroben2yl-(2 -methyl)] aniline-4-oxo-4,5-dihydrofuran3-carboxylate (JOT01007) have been tested in mouse leukemia WEHI-3 cells. In this study, the mechanisms by which JOT01007 acts on a human cervical cancer cell line (Ca Ski) to bring about an increase in the ratio of Bax/Bcl-2, reduction of the mitochondrial membrane potential (MMP), increase in the levels of cytoplasmic Ca2+, activation of caspases and fragmentation of DNA, and apoptosis were investigated. Flow cytometric analysis demonstrated that JOT01007 induced a decrease of MMP in Ca Ski cells. JOT01007 induced an increase in the level of cytoplasmic Ca2+, which was inhibited by BAPTA (calcium chelator), and BAPTA accelerated the MMP reduction, and significantly blocked JOT01007-induced apoptosis. Western blotting demonstrated that JOT01007 induced an increase in the levels of p53, p21, cytochrome-c, caspase-3 and Bax, but decreased the level of Bcl-2. In conclusion, our data demonstrate that JOT01007-induced apoptosis occurs via a mitochondria-dependent pathway closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.