Silymarin and its major constituent, Silibinin, are extracts from the medicinal plant Silybum marianum (milk thistle) and have traditionally been used for the treatment of liver diseases. Recently, these orally active, flavonoid agents have also been shown to exert significant anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas. The aim of the present review is to examine the pharmacokinetics, mechanisms, effectiveness and adverse effects of silibinin's anti-cancer actions reported to date in pre-clinical and clinical trials. The review will also discuss the results of current research efforts seeking to determine the extent to which the effectiveness of silibinin as an adjunct cancer treatment is influenced by such factors as histologic subtype, hormonal status, stromal interactions and drug metabolising gene polymorphisms. The results of these studies may help to more precisely target and dose silibinin therapy to optimise clinical outcomes for oncology patients.

BACKGROUND Resistance to apoptosis remains a significant problem in the treatment of prostate cancer. Heat‐shock proteins (HSP) have been correlated with tumor progression. The role of HSP in prostate cancer resistance to apoptosis is unknown. METHODS PC‐3 and LNCaP prostate cancer cells were heat‐shocked and then treated with or without diethyl‐maleate, etoposide, cycloheximide, or 3 Gray irradiation. Percent apoptosis was assessed by propidium iodide DNA incorporation. Protein was also extracted for analysis by SDS‐PAGE Western blotting. RESULTS Western blotting confirmed an increase in HSP 27 and 72. These cells were resistant to both chemical‐ and radiation‐induced apoptosis. Cycloheximide and specific oligonucleotides to HSP 72 blocked the increased expression of HSP 72 and the resistance to apoptosis. Mcl‐1, Bcl‐2, Bcl‐XL, and glutathione‐S‐transferase (GST) expression were increased in a time‐dependent manner after heat shocke. CONCLUSIONS This study demonstrates that HSP expression, specifically HSP 72, inhibits apoptosis in prostate tumor cell lines, which may be mediated by the production of survival factors. Prostate 45:58–65, 2000. © 2000 Wiley‐Liss, Inc.

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