This Article Full Text Full Text (PDF) Supplementary Data Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Muguruma, H. Articles by Sone, S. Search for Related Content PubMed PubMed Citation Articles by Muguruma, H. Articles by Sone, S.

Reveromycin A Inhibits Osteolytic Bone Metastasis of Small-Cell Lung Cancer Cells, SBC-5, through an Antiosteoclastic Activity

Authors' Affiliations: Departments of ¹ Internal Medicine and Molecular Therapeutics and ² Molecular and Environmental Pathology, University of Tokushima Graduate School, Tokushima, Japan and ³ Antibiotics Laboratory, Discovery Research Institute, RIKEN, Saitama, Japan

Requests for reprints: Saburo Sone, Department of Internal Medicine and Molecular Therapeutics, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, 770-8503 Tokushima, Japan. Phone: 81-88-633-7127; Fax: 81-88-633-2134; E-mail: ssone{at}clin.med.tokushima-u.ac.jp.

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.

This article has been cited by other articles:

				M. Kawatani, H. Okumura, K. Honda, N. Kanoh, M. Muroi, N. Dohmae, M. Takami, M. Kitagawa, Y. Futamura, M. Imoto, et al. The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I PNAS, August 19, 2008; 105(33): 11691 - 11696. [Abstract] [Full Text] [PDF]