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


Authors: Coffey, D. C.; Kutko, M. C.; Glick, R. D.; Butler, L. M.; Heller, G.; Rifkind, R. A.; Marks, P. A.; Richon, V. M.; La Quaglia, M. P.
Article Title: The histone deacetylase inhibitor, CBHA, inhibits growth of human neuroblastoma xenografts in vivo, alone and synergistically with all-trans retinoic acid
Abstract: 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.
Keywords: controlled study; unclassified drug; histone deacetylase inhibitor; dose response; drug efficacy; drug potentiation; nonhuman; antineoplastic agents; animal cell; mouse; animals; mice; cell division; antineoplastic combined chemotherapy protocols; animal experiment; animal model; weight loss; weight reduction; tumor xenograft; dose-response relationship, drug; mice, scid; tumor cells, cultured; xenograft model antitumor assays; drug synergism; neuroblastoma; enzyme inhibitors; cell transformation; histones; histone deacetylases; retinoic acid; scid mouse; acetylation; cinnamic acid derivative; cinnamates; growth inhibition; growth inhibitors; tretinoin; humans; human; female; priority journal; article; 3 carboxycinnamic acid bishydroxamide
Journal Title: Cancer Research
Volume: 61
Issue: 9
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2001-05-01
Start Page: 3591
End Page: 3594
Language: English
PUBMED: 11325825
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus