Pure Flavonolignans from Extracts of Milk Thistle (Silybum marianum) Against Models of Human Prostate Cancer

Milk thistle extracts have been used since antiquity for gastrointestinal ailments and in hepatoprotection against natural and pharmaceutical toxicants. Over the last ten years, the milk thistle extracts silymarin and silibinin have been recognized for significant cancer chemopreventive and anticancer activities in several animal models of human epithelial malignancies. Our research team has been interested in answering the question of whether pure compounds from milk thistle extracts possess unique or more potent anticancer effects than the mixtures commonly used in the literature. As a result, we have been isolating pure silybin A, silybin B, isosilybin A, and isosilybin B for in vitro experiments in human prostate carcinoma cell lines. Cumulative results point to isosilybin B as the most potent and effective inhibitor of PSA suppression and trigger of androgen receptor degradation in androgen-dependent cells, and inhibitor of androgen-dependent and -independent prostate cancer cell growth. To investigate the relative in vivo efficacy of these compounds in human tumor xenograft models of prostate cancer, a large-scale preparative scheme using a hybrid chromatographic/precipitative method was implemented to provide gram quantities of each pure diastereoisomer; in vivo studies with these compounds are ongoing. Taken together, isosilybin B, which is present in silymarin but absent from silibinin, may represent a unique opportunity for further development of anticancer strategies using milk thistle. Acknowledgement: These studies were supported by NIH grant R01 CA104286 to DJK and RA.