Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Lodz, Poland.
Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.
Anticancer Agents Med Chem. 2020;20(15):1787-1796. doi: 10.2174/1871520620666191220142741.
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.
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.
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.
水飞蓟宾（SB）是水飞蓟素（SM）的主要成分，是从奶蓟草种子中提取的天然物质。SM 含有高达 70%的 SB，分为 A 和 B 两种异构体。它对肝细胞具有抗氧化和抗炎作用，已知可抑制细胞增殖、诱导细胞凋亡和抑制血管生成。SB 对多种癌症具有活性，如皮肤癌、肝癌、肺癌、膀胱癌和乳腺癌。
本综述介绍了 SM 在乳腺癌中的应用，乳腺癌是女性最常见的癌症之一。它描述了 SM 作用的某些分子机制；例如，尽管 SB 影响雌激素受体（ER）α和β，但对两者的影响相反。它对 ERα 的作用影响 PI3K/AKT/mTOR 和 RAS/ERK 信号通路，而通过上调 ERβ，它增加了凋亡细胞的数量。此外，ERα 参与 SB 诱导的自噬，而 ERβ 不参与。有趣的是，SB 还通过抑制 TGF-β2 的表达来抑制上皮间质转化（EMT）来抑制转移。它还通过 Jak2/STAT3 途径影响迁移和侵袭潜能。
SB 可能是治疗乳腺癌的一种很有前途的方法：当与顺铂、卡铂和多柔比星等化疗药物联合使用时，该联合对癌细胞具有协同作用。这对于治疗侵袭性乳腺癌可能具有价值。
综上所述，SB 通过多种机制抑制增殖、诱导凋亡和抑制转移。SB 与不同的抗癌药物联合使用是一种很有前途的治疗策略，适用于患有乳腺癌的患者。
