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.
The cytotoxic effects of a new compound, ethyl 2-[N-p-chlorobenzyl-(2'-methyl)] aniline-4-oxo-4,5-dihydrofuran-3-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, p2I, 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.
Lin
Tsung-Ping
TP
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC.
Huang
An-Cheng
AC
Wei
Hsiu-Chuan
HC
Lin
Jaung-Gung
JG
Chung
Jing-Gung
JG
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002264:Carboxylic Acids; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D005663:Furans; C521182:ethyl-2-(N-p-chlorobenzyl-(2'-methyl))anilino-4-oxo-4,5-dihydrofuran-3-carboxylate; D002118:Calcium