Abstract
β-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 β-lapachone, at concentrations of less than 8 µm, induces cell death with characteristics of apoptosis in human prostate cancer cell lines. This effect of β-lapachone was also observed in a human promyelocytic leukemia cell line (HL-60). β-Lapachone-induced apoptosis is independent of p53 expression, and ectopic overexpression of bcl-2 did not confer significant resistance to β-lapachone. Among other human carcinoma and adenoma cell lines tested, human breast and ovary carcinoma showed sensitivity to the cytotoxic effect of β-lapachone without manifesting signs of apoptosis. These results suggest that β-lapachone is a potential compound to be added to cancer chemotherapy, particularly for prostate cancer.
This work was supported by NIH Grant AI-35511.