Characteristics of mitotic cell death induced by enediyne antibiotic lidamycin in human epithelial tumor cells.
Mitotic cell death, a different cell death mode from apoptosis, has been focused on in tumor therapy. It may involve the mechanism of highly potent cytotoxicities of enediyne antibiotics toward tumor cells. We describe the characteristics of mitotic cell death induced by enediyne antibiotic lidamycin at low concentrations (0.01-1 nM), in the human hepatoma BEL-7402 cells and human breast carcinoma MCF-7 cells. The cells exerting mitotic cell death showed retardation at G2+M phase, enlargement of cell volume and multinucleation, some of which were positive in senescence-associate beta-galactosidase staining. The multinucleated living cells did not show apoptotic features by co-staining with mitochondria-specific dye Mitosensor and DNA-specific dye Hoechst 33342. The DNA polyploidy rather than <apoptotic sub-G1 peak> increased with incubation time for the lidamycin-treated BEL-7402 cells. The proliferation status of BEL-7402 cells was shown by flow cytometry after the cells were labeled with PKH-67, a fluorescent dye for labeling living cells, but the fluorescent intensity of the lidamycin-treated cells was little changed. The smear DNA pattern was detected in the multinucleated cells by agarose gel electrophoresis. The results provide the first evidence for elucidating the potent cytotoxicities of lidamycin toward tumor cells and further describing characteristics of mitotic cell death.
He
Qi Yang
QY
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, P.R. China.
Liang
Yun Yan
YY
Wang
Dai Shu
DS
Li
Dian Dong
DD
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D053281:Enediynes; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008938:Mitosis / Q000187:drug effects* / Q000235:genetics; D011123:Polyploidy; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004273:DNA, Neoplasm; D053281:Enediynes; C058024:C 1027