Cancers, Vol. 11, Pages 1637: Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3 β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo

Cancers, Vol. 11, Pages 1637: Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo Cancers doi: 10.3390/cancers11111637 Authors: Andrew K. Kwegyir-Afful Senthilmurugan Ramalingam Vidya P. Ramamurthy Puranik Purushottamachar Francis N. Murigi Tadas S. Vasaitis Weiliang Huang Maureen A. Kane Yuji Zhang Nicholas Ambulos Sudhir Tiwari Pratima Srivastava Ivo P. Nnane Arif Hussain Yun Qiu David J. Weber Vincent C. O. Njar These studies compared the efficacies of our clinical agent galeterone (Gal) and the FDA-approved prostate cancer drug, enzalutamide (ENZ) with two lead next generation galeterone analogs (NGGAs), VNPP414 and VNPP433-3β, using prostate cancer (PC) in vitro and in vivo models. Antitumor activities of orally administered agents were also assessed in CWR22Rv1 tumor-bearing mice. We demonstrated that Gal and NGGAs degraded AR/AR-V7 and Mnk1/2; blocked cell cycle progression and proliferation of human PC cells; induced apoptosis; inhibited cell migration, invasion, and putative stem cell markers; and reversed the expression of epithelial-to-mesenchymal transition (EMT). In addition, Gal/NGGAs (alone or in combination) also inhibited the growth of ENZ-, docetaxel-, and mitoxantrone-resistant human PC cell lines. The NGGAs exhibited improved pharmacokinetic profiles over Gal i...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research