Induction of Apoptosis by ß-Lapachonein Human Prostate Cancer Cells1

ß-Lapachone, a plant product, has been shown to be a novel inhibitor of DNA topoisomerase I, with a mode of action different from camptothecin and a chemical structure distinct from those of current anti-cancer drugs. We observed that ß-lapachone, at concentrations of less than 8 UM, induces cell death with characteristics of apoptosis in human prostate cancer cell lines. This effect of ß-lapachone was also observed in a human promyelocytic leukemia cell line (III.-60). ß-Lapachone-induced apoptosis is independent of p53 expression, and ectopie overexpression of bcl-2 did not confer significant resistance to ß-lapa chone. Among other human carcinoma and adenoma cell lines tested, human breast and ovary carcinoma showed sensitivity to the cytotoxic effect of ß-lapachone without manifesting signs of apoptosis. These results suggest that ß-lapachone is a potential compound to be added to cancer chemotherapy, particularly for prostate cancer.