Abstract
Abstract Prostate cancer (PCa) is the second leading cause of cancer deaths in men, and the majority of prostate cancer deaths are a result of emergence of castrate resistant phenotype. Our previous studies indicated that Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the root of Stephania tetrandra inhibited cell cycle progression and promoted growth arrest at lower concentrations and promoted apoptosis at higher concentrations and at longer time points. AR signaling is known to play a critical role in androgen responsive prostate cancer cells. In the present studies we evaluated the effects of TET on AR signaling in androgen dependent (LNCaP cells) as well as castrate resistant (C4 and C42B cells, castrate resistant lineages of LNCaP cells) prostate cancer cells. Exposure of LNCaP cells to Tet resulted in a dose and time dependent decrease in PSA protein (cell associated as well as secreted PSA). Further analysis revealed that Tet also decreased PSA mRNA as well as PSA promoter activity, suggesting that Tet induced decrease in PSA was a result of inhibition of PSA transcription. Since PSA is known to be an AR responsive gene, these results led us to investigate the effects of Tet on AR signaling. Results from these studies revealed that Tet inhibited AR activity as measured by TARP promoter assay. Taken together these studies suggest that Tet targets AR signaling pathway effectively blocking AR target genes. In summary our results suggest that Tet by inhibiting AR signaling pathway may work as an effective therapeutic agent in prostate cancer, for which there is no cure to date. Grant Support: Studies supported in part by VA Merit Award-01BX001258 (HK), NIH/NCI R01CA161880 (HK) and Department of Surgery, School of Medicine chair commitment (HK). Citation Format: Sweaty Koul, Hari K. Koul. Tetrandrine impairs prostate cancer cell survival in part by inhibiting AR signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2123. doi:10.1158/1538-7445.AM2013-2123
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