Apoptotic death mode of mitomycin C-treated HeLa cells and cellular localization of mitomycin C-induced P-glycoprotein.
Mitomycin C (MMC) is an active antineoplastic agent and is suggested to induce apoptosis in a caspase- dependent manner in human gastric, bladder, and breast cancer cells. In this study, the death mode of human cervical cancer cells (HeLa) induced by MMC and the cellular localization of MMC-induced P-glycoprotein (P-gp) were investigated. The results of caspase-3 activity, Annexin V binding, and DNA fragmentation suggested that the degree of caspase-dependent apoptosis induced by MMC was in a dose-, but not time-dependent, manner. Further, in low-dose (0.0299 microM) and long-term (2 months) treatment with MMC, P-gp is itself extruded from the cells and colocalized with nuclear DNA and the overexpression was achieved.
Cheng
Min-Hsiung
MH
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan, ROC.
Cheng
Hao-Tsai
HT
Lin
Shih-Shen
SS
Young
Su-Chung
SC
Pai
Chien-Jung
CJ
Liao
Pao-Hsin
PH
Chen
Shu-Chen
SC
Chou
Ming-Yung
MY
Yang
Jaw-Ji
JJ
Yang
Chi-Chiang
CC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008297:Male; D016685:Mitomycin / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017304:Annexin A5; D016685:Mitomycin