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 act ivity to induce apoptosis of tumor cells. Doxorubicin and daunorubicin, rad iomimetic anthracycline-group drugs, have been used for chemotherapy for ab out 30 years. Here we established the colorectal tumor and osteosarcoma cel ls in which Bar expression can be induced by the treatment of isopropyl-bet a-D-thiogalactopyranoside, and examined the effect of the Bar overexpressio n on the cell death caused by these drugs. While the Bar overexpression nei ther affected growth nor morphology of the undamaged cells, it enhanced the cell death caused by these drugs. Increase in cellular nucleus fragmentati on and DNA ladder formation indicates that the Bar-enhanced cell death is d ue to enhanced apoptosis of the drug-treated cells. The enhanced cell death was nor observed when the cells were irradiated with X-ray or treated with other chemotherapeutic agents we examined. These results indicate that Bar may have a specific role to enhance the efficacy of chemothrapy with anthr acycline-group agents.