Tetrandrine (Tet) is a naturally derived bis-benzylisoquinoline alkaloid, from S tenrandra, a herb that has been used in Chinese medicine for its anti-inflammatory, immunologic and antiallergenic effects. Results from our laboratory show that Tetrandarine blocks prostate cancer growth, promotes cell cycle arrest and induces apoptosis in a time and concentration dependent manner. In the present study we performed un-biased gene expression analysis of LNCaP cells following treatment with Tet. Analysis of gene expression revealed that GDF-15 was one of the most highly expressed cytokines following treatment of LNCaP cells with Tet. The gene expression results were further confirmed in relative quantitative PCR and Real time PCR assays, as was protein expression of GDF-15 confirmed by Western blot analysis. Our results, in light of the role of GDF-15 as a macrophage inhibitory factor as well as prostate epithelial differentiating factor, suggest that Tet may serve as a useful agent to promote prostate epithelial differentiation and inhibit tumor macrophage infiltration. Additional studies revealed that Treatment of PCa cells with Tet inhibited cell migration and invasion and suppressed EMT. Taken together we conclude that Tet by regulating GDF-15 expression may serve as an inhibitor of Prostate cancer cell progression and metastasis.
(Financial Support: Supported in part by NIH/NCI R01CA161880 (PI:H.Koul); VA Merit Award 01BX001258 (PI:H.Koul); Carroll W. Feist endowed Cahir and LSUHSC Chair Commitment Funds)
Citation Format: Sweaty Koul, Hari K. Koul. Tetrandrine induces expression of growth/differentiation factor-15 and promoted terminal differentiation of PCa cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1122. doi:10.1158/1538-7445.AM2014-1122