Oral administration of withaferin A inhibits carcinogenesis of prostate in TRAMP model

• DOI: 10.18632/oncotarget.10733
• Publication Date: 2016-07-20T12:11:21Z
• Authors: Suman Suman; Trinath P. Das; Jim Moselhy; Deeksha Pal; Venkatesh Kolluru; Houda Alatassi; Murali K. Ankem; Chendil Damodaran
• Keywords: Tramp; Withaferin A

// Suman 1 , Trinath P. Das Jim Moselhy Deeksha Pal Venkatesh Kolluru Houda Alatassi 2 Murali K. Ankem Chendil Damodaran Department of Urology, University Louisville, KY, USA Pathology, Correspondence to: Damodaran, email: [e-mail] Keywords: dietary agents, chemoprevention, prostate cancer Received: April 28, 2016 Accepted: June 13, Published: July 20, ABSTRACT We previously reported that withaferin A (WA), a natural compound, deters by inhibiting AKT while inducing apoptosis. In the current study, we examined its chemopreventive efficacy against carcinogenesis in using transgenic adenocarcinoma mouse (TRAMP) model. Two distinct sets experiments were conducted. To determine whether WA delays tumor progression, it was given before onset, at week 6, and until 44. effect after onset cancer, from weeks 12 to 35. both strategies, oral administration effectively suppressed burden when compared vehicle-treated animals. No toxicity seen treated animals gross pathological examination. Western blot analysis immunohistochemistry sections revealed TRAMP controls, pAKT highly expressed nuclear FOXO3a Par-4 downregulated. On contrary, mice showed inhibition signaling activation FOX03a-Par-4-induced cell death. They also displayed mesenchymal markers such as β-catenin, vimentin, snail well upregulation E-cadherin. Because expressions angiogenic factor VIII retic downregulated, an anti-angiogenic role is suggested. Overall, our results suggest could be promising anti-cancer agent inhibits prostate.