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

[ Vol. 20 , Issue. 15 ]

Author(s):

Agata Binienda, Sylwia Ziolkowska and Elzbieta Pluciennik*   Pages 1787 - 1796 ( 10 )

Abstract:


<P>Background: Silibinin (SB), the main component of Silymarin (SM), is a natural substance obtained from the seeds of the milk thistle. SM contains up to 70% of SB as two isoforms: A and B. It has an 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. </P><P> Methods: 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), &#945; and &#946;, it has opposite effects on the two. Its action on ERĪ± influences the PI3K/AKT/mTOR and RAS/ERK signaling pathways, while by up-regulating ER&#946;, it increases the numbers of apoptotic cells. In addition, ER&#945; is involved in SB-induced autophagy, while ER&#946; is not. Interestingly, SB also inhibits metastasis by suppressing TGF-&#946;2 expression, thus suppressing Epithelial to Mesenchymal Transition (EMT). It also influences migration and invasive potential via the Jak2/STAT3 pathway. </P><P> Results: 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. </P><P> Conclusion: Summarizing, SB inhibits proliferation, induces apoptosis, and restrains metastasis via several mechanisms. It is possible to combine SB with different anticancer drugs, an approach that represents a promising therapeutic strategy for patients suffering from BC.</P>

Keywords:

Silibinin, estrogen, estrogen receptors, signaling pathways, breast cancer, metastasis.

Affiliation:

Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Lodz, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Lodz, Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz

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