Anti-cancer effects of silibinin: The current status in cancer chemoprevention

Abstract

The naturally occurring flavonolignan Silibinin (also known as Silybin) is a bioactive constituent of silymarin isolated from the seeds of the milk thistle plant (Silybum marianum L. Gaernt.), a member of the Asteraceae family. The milk thistle plant is a part of the native vegetation in Southern Europe, Southern Russia, Asia Minor and Northern Africa. This multi-functional flavonolignan possesses strong hepatoprotective, cardioprotective, neuroprotective, immune-modulatory, antidotal and anti-neoplastic properties. To date, over 600 peer-reviewed research reports and limited clinical trials have evaluated the anti-oncogenic efficacy of silibinin to combat tumor growth, angiogenesis, and metastasis. As a promising agent, silibininmediates a wide-range of potent chemopreventive and anti-cancer activities in several frequently diagnosed epithelial malignancies, including skin, colon, prostate and lung. In addition, several combinatorial anti-cancer strategies of silibinin with other therapeutics exhibit synergistic interactions to suppress drug-induced toxic effects and chemoresistance. In this chapter, the pre-clinical and clinical efficacy of silibinin and/or silymarin derivatives against several cancers will be reviewed. Moreover, the chapter will summarize silibinin effects on key signaling pathways, such as: transforming Growth Factor beta (TGFβ), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), and NF-κB (nuclear factor-kappa B), which are crucial to the anti-cancer activity of silibinin in cancer prevention, disease progression/recurrence and reversal of drug resistance.