Apoptotic death mode of mitomycin C-treated HeLa cells and cellular localization of mitomycin C-induced P-glycoprotein

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2009-04, Vol.32 (2), p.158-168
• Main Authors: Cheng, Min-Hsiung, Cheng, Hao-Tsai, Lin, Shih-Shen, Young, Su-Chung, Pai, Chien-Jung, Liao, Pao-Hsin, Chen, Shu-Chen, Chou, Ming-Yung, Yang, Jaw-Ji, Yang, Chi-Chiang
• Format: Article
• Language: English
• Subjects: Annexin A5 - metabolism; Antineoplastic agents; Apoptosis; Apoptosis - drug effects; ATP Binding Cassette Transporter, Subfamily B, Member 1 - drug effects; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Biological and medical sciences; Cell Death - drug effects; Cell Line, Tumor; Cells, Cultured; Chemotherapy; confocal microscopy; DNA Fragmentation - drug effects; HeLa cell; HeLa Cells; Humans; Male; Medical sciences; Mitomycin - pharmacology; mitomycin C; P-glycoprotein; Pharmacology. Drug treatments
• ISSN: 0148-0545; 1525-6014
• DOI: 10.1080/01480540802594491

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 μM) 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.