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¹ Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California; ² Department of Medicine, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California; and ³ Laboratory of Medicinal Chemistry, Center for Cancer Research, NIH, Frederick, Maryland

Requests for reprints: Nouri Neamati, Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089. Phone: 323-442-2341; Fax: 323-442-1390. E-mail: neamati{at}usc.edu

We discovered a series of salicylhydrazide class of compounds with remarkable anticancer activity against a panel of hormone receptor–positive and -negative cell lines. In the present study, we evaluated the in vitro activity of SC21 and SC23 against a range of human tumor cell types and the in vivo efficacy of compound SC21 in a PC3 human prostate cancer xenograft model in mice. We also determined the effects of SC21 on cell cycle regulation and apoptosis. Our in vitro results show that salicylhydrazides are highly potent compounds effective in both hormone receptor–positive and -negative cancer cells. SC21 induced apoptosis and blocked the cell cycle in G₀/G₁ or S phase, depending on the cell lines used and irrespective of p53, p21, pRb, and p16 status. SC21 effectively reduced the tumor growth in mice without apparent toxicity. Although the mechanism of action of SC21 is not completely elucidated, the effect on cell cycle, the induction of apoptosis and the activity against a panel of tumor cell lines of different origins prompted us to carry out an in-depth preclinical evaluation of SC21.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁴ N. Neamati, C. Plasencia, and R. Dayam, unpublished.

Received 10/28/04; revised 4/20/05; accepted 5/ 4/05.