Studies from Ohio State University, Comprehensive Cancer Center describe new findings in hepatocellular cancer therapy
2007 NOV 19 -- Scientists discuss in 'Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma' new findings in hepatocellular cancer. "Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, yet effective therapeutic options for advanced HCC are limited. This study was aimed at assessing the antitumor effect of a novel phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, OSU-HDAC42, vis-à-vis suberoylanilide hydroxamic acid (SAHA), in in vitro and in vivo models of human HCC," investigators in the United States report. "OSU-HDAC42 was several times more potent than SAHA in suppressing the viability of PLC5, Huh7, and Hep3B cells with submicromolar median inhibitory concentration (IC(50)) values. With respect to SAHA, OSU-HDAC42 exhibited greater apoptogenic potency, which was associated with reduced levels of the apoptotic regulators phosphorylated Akt B-cell lymphoma-xL, survivin, cellular inhibitor of apoptosis protein 1, and cellular inhibitor of apoptosis protein 2. The in vivo efficacy of OSU-HDAC42 versus SAHA was assessed in orthotopic and subcutaneous xenograft tumor models in athymic nude mice. Daily oral treatments with OSU-HDAC42 and SAHA, both at 25 mg/kg, suppressed the growth of orthotopic PLC5 tumor xenografts by 91% and 66%, respectively, and of established subcutaneous PLC5 tumor xenografts by 85% and 56%, respectively. This differential tumor suppression correlated with the modulation of intratumoral biomarkers associated with HDAC inhibition and apoptosis regulation," wrote Y.S. Lu and colleagues, Ohio State University, Comprehensive Cancer Center. The researchers concluded: "Moreover, the oral administration of OSU-HDAC42 at 50 mg/kg every other day markedly suppressed ectopic tumor growth in mice bearing large tumor burdens (500 mm(3)) at the start of treatment OSU-HDAC42 is a potent, orally bioavailable inhibitor of HDAC with a broad spectrum of antitumor activity that includes targets regulating multiple aspects of cancer cell survival. These results suggest that OSU-HDAC42 has clinical value in therapeutic strategies for HCC." Lu and colleagues published their study in Hepatology (Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma. Hepatology, 2007;46(4):1119-30). For additional information, contact Y.S. Lu, College of Pharmacy and Comprehensive Cancer Center, Division of Medicinal Chemistry and Pharmacognosy, Ohio State University, Columbus, OH 43210 USA.. The publisher of the journal Hepatology can be contacted at: John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA. Keywords: United States, Columbus, Hepatocellular Cancer Therapy, Apoptosis, Deacetylase, Enzyme Research, Hepatocellular Cancer, Hepatocellular Carcinoma, Hepatology, Oncology, Therapy, Treatment. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
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