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Induction of Apoptosis by ß-Lapachone in Human Prostate Cancer Cells¹

Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

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 µM, 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 (HL-60). ß-Lapachone-induced apoptosis is independent of p53 expression, and ectopic overexpression of bcl-2 did not confer significant resistance to ß-lapachone. 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.

¹ This work was supported by NIH Grant AI-35511.

² To whom requests for reprints should be addressed, at Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 6/14/95. Accepted 7/21/95.

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