The Anticancer Properties of Silibinin: its Molecular Mechanism and Therapeutic Effect in Breast Cancer.

Silibinin (SB), the main component of silymarin (SM) is a natural substance obtained from the seeds of the milk thistle. SM contains up 70% of SB as two isoforms: A and B. It has antioxidant and anti-inflammatory effect on hepatocytes, and is known to inhibit cell proliferation, induce apoptosis and curb angiogenesis. SB has demonstrated activity against many cancers, such as skin, liver, lung, bladder and breast carcinomas.This review presents current knowledge of the use of SM in breast cancer, this being one of the most common types of cancer in women. It describes selected molecular mechanisms of the action of SM; for example, although SB influences both estrogen receptors (ER), α and β, it has opposite effects on the two. Its action on ERα influences the PI3K/AKT/mTOR and RAS/ERK signaling pathways, while by up-regulating ERβ, it increases the numbers of apoptotic cells. In addition, ERα is involved in SB-induced autophagy, while ERβ is not. Interestingly, SB also inhibits metastasis by suppressing TGF-β2 expression, thus suppressing epithelial to mesenchymal transition (EMT). It also influences migration and invasive potential via the Jak2/STAT3 pathway.SB may be a promising enhancement of BC treatment: when combined with chemotherapeutic drugs such as carboplatin, cisplatin and doxorubicin, the combination exerts a synergistic effect against cancer cells. This may be of value when treating aggressive types of mammary carcinoma.