Abstract A58: Characterized herbal extract of Wedelia chinensis suppresses prostate cancer growth and metastasis by targeting multiple intrinsic pathways and modulating immune cells

Abstract

Abstract We previously demonstrated that the principal active compounds (wedelolectone, luteolin, and apigenin) in the ethanol extract of Wedelia chinensis synergistically inhibit human prostate carcinoma 22Rv1 cell growth and that this extract therefore has potential for use as a prostate cancer (PCa) therapy. Here, we developed a standardized preparation for a W. chinensis ethanol extract that is enriched in the principal active compounds. A comparison of the effect of herbal treatment, androgen ablation therapy, and a combination of the two on the development of androgen-dependent LNCaP tumors in a mouse model showed that the herbal extract alone decreased androgen-induced tumor growth and when in combination with androgen ablation therapy, resulted in more potent inhibition of both tumor growth and cancer metastasis. Our study demonstrated this herbal remedy simultaneously inhibited androgen receptor, NFκB and HER2/3-AKT signaling pathways to induce cell apoptosis. Importantly, our herbal remedy diminished androgen receptor overexpression and AKT activation induced by androgen ablation thus preventing castration-resistant PCa development. Moreover, the herbal remedy standing-alone curbed chemokine expression from hormone-refractory PC-3 tumor and consequently restrained the mobilization of CD11b+Gr1+ myeloid cells in tumor-bearing mice, which effectively inhibited PCa growth and metastasis. In conclusion, this standardized preparation of W. chinensis ethanol extract improved the outcome of PCa therapy either as an add-on to hormonal therapy for androgen-dependent disease or as a monotherapy for hormone-refractory disease. Citation Format: Chin-Hsien Tsai, Sheue-Fen Tzeng, Pei-Wen Hsiao. Characterized herbal extract of Wedelia chinensis suppresses prostate cancer growth and metastasis by targeting multiple intrinsic pathways and modulating immune cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A58. doi:10.1158/1538-7445.CHTME14-A58