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Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity.

Muguruma H, Yano S, Kakiuchi S, Uehara H, Kawatani M, Osada H, Sone S

Department of Internal Medicine and Molecular Therapeutics, University of Tokushima Graduate School, Tokushima, and Antibiotics Laboratory, Discovery Research Institute, RIKEN, Saitama, Japan.

PURPOSE: The purpose of this study was to determine therapeutic effect of a novel antibiotic, reveromycin A, against osteolytic bone metastasis of human small cell lung cancer (SBC-5) cells. RESULTS: Reveromycin A induced apoptosis specifically in osteoclasts in vitro. Although reveromycin A did not inhibit SBC-5 cell proliferation, it suppressed the expression of parathyroid hormone-related peptide. Intravenous inoculation of SBC-5 cells in natural killer cell-depleted severe combined immunodeficient mice produced experimental metastases in multiple organs, including the bone. Daily administration of reveromycin A inhibited the bone metastasis, but not visceral metastasis, in a dose-dependent manner. Histologic analyses revealed that although treatment with reveromycin A did not affect the number of proliferating tumor cells, it decreased the number of osteoclasts and increased apoptotic cells in bone lesions. CONCLUSIONS: These findings suggest that reveromycin A may inhibit osteolytic bone metastasis through suppression of osteoclast activity by directly inducing apoptosis and indirectly inhibiting tumor cell-derived parathyroid hormone-related peptide production. Therefore, reveromycin A may be a novel, potent therapeutic agent against osteolytic bone metastasis of lung cancer in humans.

Published 19 December 2005 in Clin Cancer Res, 11(24): 8822-8.
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