[Effects of lidamycin on apoptotic gene expressions and cytoskeleton in human hepatoma bel-7402 cells].
OBJECTIVE
Lidamycin, one of enediyne antitumor antibiotics, was isolated by our institute. It is the focus of intense due to its unique chemical structure and potent cytotoxicities to tumor cells in vivo and in vitro. In addition to cleavage of DNA, effect of lidamycin on apoptotic gene expressions and cytoskeleton may involve in its high activities. To further elucidate its mechanism, we have observed the effect of lidamycin on the above-mentioned factors in human hepatoma bel-7402 cells.


METHODS
The gene expressions were determined by Northern blot and dot blotanalysis. The changes of microfilament and microtubule were detected by indirect immunofluorescent method and the apoptotic cells were detected with mitochondria-specific apoptotic dye Mitosensor.


RESULTS
The obvious increment of c-myc and c-fos gene expressions and the inhibition of N-ras gene expression in bel-7402 cells were observed following lidamycin treatment (0.1-10 nmol/L) for 8 h. The arrangement of microfilament in the cells became regular and was similar to nonmalignant normal cells, but there was no effect on microtubule when the bel-7402 cells were treated with lidamycin 10 nmol/L for 8 h. No apoptotic cells were detected with Mitosensor in the lidamycin-treated cells for 8 h.


CONCLUSIONS
Lidamycin at lower concentrations can markedly affect the expression of the apoptosis related genes and the distribution of the cytoskeleton in the hepatoma bel-7402 cells. The results are helpful to elucidate the molecular mechanism of potent cytotoxicities of lidamycin to tumor cells.
He
Qi-yang
QY
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, P. R. China.
Jiang
Bing
B
Li
Dian-dong
DD
Zhen
Yong-su
YS
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects*; D053281:Enediynes; D015870:Gene Expression / Q000187:drug effects*; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; C058024:C 1027