[Characterization of cell death induced by anticancer antibiotic lidamycin in human hepatoma BEL-7402 cells].
OBJECTIVE
To study the features of cell death induced by the anticancer antibiotic lidamycin (LDM) in human hepatoma BEL-7402 cells.


METHODS
Chromatin condensation was observed by co-staining with fluorescent dyes, hoechst 33342 and propidium iodide. "G1 sub-peak" was detected by flow cytometry and DNA ladder was observed using agarose gel electrophoresis. The caspase-3, 6 activities were measured with kits specific for them.


RESULTS
Typical apoptotic chromatin condensations appeared when the BEL-7402 cells were treated with the conventional antitumor agent mitomycin C30 mumol.L-1 for 12 h. However, an abnormal type of chromatin condensation occurred when the cells were treated with LDM 1 mumol.L-1 for 6 h, which was characterized with keeping the completeness of nuclear membrane and not forming apoptotic bodies. The DNA ladder patterns were observed using agarose gel electrophoresis. The "G1 sub-peak" occurred only in the cells treated with LDM for 24 h, though chromatin condensation was earlier detected in treatment with LDM for 6 h. The caspase-3, 6 activities were increased about 5 and 4 folds, after the cells were treated with LDM 1 mumol.L-1 for 6 h, as did mitomycin C. The time of initiating chromatin condensation was earlier than that of the high peak activities of caspase-6.


CONCLUSIONS
The characterization of cell death induced by lidamycin in the human hepatoma BEL-7402 cells differs from typical apoptosis. The results make it helpful to explain the molecular mechanism of the highly potent cytotoxicities of lidamycin toward tumor cells.
He
Q Y
QY
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Liang
Y Y
YY
Wang
D S
DS
Li
D D
DD
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases / Q000378:metabolism; D053281:Enediynes; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; C058024:C 1027; C505407:CASP3 protein, human; C505514:CASP6 protein, human; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases