Apoptosis of human tumor cells by chemotherapeutic anthracyclines is enhanced by Bax overexpression.
One of the major factors for efficacy of a chemotherapeutic drug is its activity to induce apoptosis of tumor cells. Doxorubicin and daunorubicin, radiomimetic anthracycline-group drugs, have been used for chemotherapy for about 30 years. Here we established the colorectal tumor and osteosarcoma cells in which Bax expression can be induced by the treatment of isopropyl-beta-D-thiogalactopyranoside, and examined the effect of the Bax overexpression on the cell death caused by these drugs. While the Bax overexpression neither affected growth nor morphology of the undamaged cells, it enhanced the cell death caused by these drugs. Increase in cellular nucleus fragmentation and DNA ladder formation indicates that the Bax-enhanced cell death is due to enhanced apoptosis of the drug-treated cells. The enhanced cell death was not observed when the cells were irradiated with X-ray or treated with other chemotherapeutic agents we examined. These results indicate that Bax may have a specific role to enhance the efficacy of chemotherapy with anthracycline-group agents.
Lu
Y
Y
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Japan.
Yagi
T
T
D018943:Anthracyclines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D018943:Anthracyclines; D000970:Antineoplastic Agents; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein