The histone deacetylase inhibitor, CBHA, inhibits growth of human neuroblastoma xenografts in vivo, alone and synergistically with all-trans retinoicacid

Histone deacetylase inhibitors (HDACIs) inhibit the growth of a variety of transformed cells in culture. We demonstrated previously that the hybrid-po lar HDACI m-carboxycinnamic acid bis-hydroxamide (CBHA) induces apoptosis o f human neuroblastoma in vitro and is effective in lower doses when combine d with retinoids, The current study investigates the effect of CBHA on the growth of human neuroblastoma in vivo, both alone and in combination with a ll-trans retinoic acid (atRA), using a severe combined immunodeficiency-mou se xenograft model. CBHA (50, 100, and 200 mg/kg/day) inhibited growth of S MS-KCN-69n tumor xenografts in a dose-dependent fashion, with 200 mg/kg CBH A resulting in a complete suppression of tumor growth. The efficacy of 50 a nd 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 resu lts suggest HDACIs alone or combined with retinoids may have therapeutic ut ility for neuroblastoma.