[Arsenic trioxide induced cell apoptosis by mitochondria dependent pathway in KB and KBv200 cells].
OBJECTIVE
Arsenic trioxide (As2O3) is a new drug used to treat the patients with solid tumor,but the mechanism is still unclear. This study was designed to investigate the effect of mitochondrial dependent pathway in apoptosis induced by arsenic trioxide in multidrug resistant KBv200 cells and their parental sensitive KB cells.


METHODS
The cytotoxic effect of As2O3 on KB and KBv200 cells was measured by MTT assay. KB and KBv200 cells were treated respectively with As2O3 for 12, 24, 48 hours. Cell apoptosis was determined by Annexin V FITC staining. Mitochondrial membrane potential was labeled by DiOC6 and examined by flow cytometry.


RESULTS
Arsenic trioxide showed the inhibition of KB and KBv200 cells proliferation in vitro. The IC(50)s of As2O3 to KB and KBv200 cells were (0.22+/-0.02)microg/ml and (0.20+/-0.01)microg/ml, respectively. As2O3 induced cell apoptosis in time- dependent manner. The apoptosis rates were 20.2%+/-3.1% and 52.2%+/-11.0% for KB cells and 15.8%+/-1.3% and 36.4%+/-5.9% for KBv200 cells under 2.5 microg/ml As2O3 treating 24 h and 48 h, respectively. The levels of mitochondrial membrane potential were concentration-dependently decreased after treating with arsenic trioxide for 12, 24, and 48 hours.


CONCLUSIONS
The decrease of mitochondrial membrane potential maybe plays an important role in apoptosis induced by As2O3.
Li
Yan-Fang
YF
Cancer Center,Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
Wang
Xu-Dong
XD
Liang
Yong-Ju
YJ
Chen
Li-Ming
LM
Ding
Yan
Y
Huang
Min
M
Fu
Li-Wu
LW
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007624:KB Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D010087:Oxides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide