The combination of the histone deacetylase inhibitor vorinostat and synthetic triterpenoids reduces tumorigenesis in mouse models of cancer.

ABSTRACT: Novel drugs and drug combinations are needed for the chemoprevention and treatment of cancer. We show that the histone deacetylase inhibitor vorinostat [suberoylanilide hydroxamic acid (SAHA)] and the methyl ester or ethyl amide derivatives of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me and CDDO-Ea, respectively) cooperated to inhibit the de novo synthesis of nitric oxide in RAW 264.7 macrophage-like cells and in primary mouse peritoneal macrophages. Additionally, SAHA enhanced the ability of synthetic triterpenoids to delay formation of estrogen receptor-negative mammary tumors in MMTV-polyoma middle T (PyMT) mice. CDDO-Me (50 mg/kg diet) and SAHA (250 mg/kg diet) each significantly delayed the initial development of tumors by 4 (P < 0.001) and 2

SUBMITTER: Tran K 

PROVIDER: S-EPMC3534195 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature