Antitumor effects of AR-42, a novel histone deacetylase inhibitor, in embryonal carcinoma.

• DOI: 10.1200/jco.2011.29.7_suppl.232
• Publication Date: 2017-02-23T18:54:21Z
• Authors: A. S. Bhinder; V. Varma; B. Abbaoui; J. M. Thomas-Ahner; S. K. Kulp; C. Chen; S. K. Clinton; A. Mortazavi
• Keywords: Histone deacetylase inhibitor; Viability assay

232 Background: Histone deacetylase inhibitors (HDACIs) modulate gene expression and induce cellular differentiation, growth inhibition apoptotic cell death by chromatin hyperacetylation. Developmental arrest of germ differentiation earlier in the life is responsible for pathogenesis tumors (GCT). With current treatment nearly 95% patients with GCT can be cured. Yet, effective agents less toxicity are desired. In addition, those relapsed/refractory disease have a dismal prognosis, indicating clear need new, more agents. Here we assess antitumor effects AR-42, novel HDACI vitro vivo models embryonal carcinoma. Methods: AR-42 suberoylanilide hydroxamic acid (SAHA) were evaluated NTERA-2, an carcinoma (EC) line derived from human testicular cancer. Cell viability (MTS assay), apoptosis (caspase 3/7 activity PARP cleavage), cycle analysis (flow cytometry) HDAC (immunoblotting) assessed. The efficacy was assessed NTERA-2 xenograft tumor model male athymic nude mice. Mice fed control diet containing at average dose 25 mg/kg/day. Tumor volumes weights used as endpoints. Results: Treatment cells both 0.1-10 μM concentrations showed time- dose-dependent reduction viability. Both significantly induced apoptosis, hyperacetylation histones H-3 H-4 manner. studies that potent than SAHA. our rodent model, AR-42-containing resulted significant (50% 56%, respectively). results intratumoral changes proliferation pending. There no toxicities associated except atrophy, known to reversible. Conclusions: appears inhibitor EC through different mechanisms, orally bioavailable well tolerated model. Our data indicates AR- 42 may clinical value requires further investigation trials. No financial relationships disclose.