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[Cancer Research 61, 3591-3594, May 1, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

The Histone Deacetylase Inhibitor, CBHA, Inhibits Growth of Human Neuroblastoma Xenografts in Vivo, Alone and Synergistically with All-Trans Retinoic Acid1

Dennis C. Coffey2, Martha C. Kutko2, Richard D. Glick, Lisa M. Butler, Glenn Heller, Richard A. Rifkind, Paul A. Marks, Victoria M. Richon and Michael P. La Quaglia3

Departments of Pediatrics [D. C. C., M. C. K.] and Surgery [R. D. G.], Joan and Sanford I. Weill Graduate School of Medical Sciences of Cornell University, and Departments of Pediatrics [D. C. C], Cell Biology [L. M. B., R. A. R., P. A. M., V. M. R.], Biostatistics [G. H.], and Pediatric Surgery [M. P. L. Q.], Sloan-Kettering Institute and Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Histone deacetylase inhibitors (HDACIs) inhibit the growth of a variety of transformed cells in culture. We demonstrated previously that the hybrid-polar HDACI m-carboxycinnamic acid bis-hydroxamide (CBHA) induces apoptosis of human neuroblastoma in vitro and is effective in lower doses when combined with retinoids. The current study investigates the effect of CBHA on the growth of human neuroblastoma in vivo, both alone and in combination with all-trans retinoic acid (atRA), using a severe combined immunodeficiency-mouse xenograft model. CBHA (50, 100, and 200 mg/kg/day) inhibited growth of SMS-KCN-69n tumor xenografts in a dose-dependent fashion, with 200 mg/kg CBHA resulting in a complete suppression of tumor growth. The efficacy of 50 and 100 mg/kg CBHA was enhanced by the addition of 2.5 mg/kg atRA. This dose of atRA was ineffective when administered alone. Treatment was accompanied by mild weight loss in all groups except the lowest dose of CBHA. Our results suggest HDACIs alone or combined with retinoids may have therapeutic utility for neuroblastoma.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.