1 Institute of Pharmacology, National Yang-Ming University , Taipei City, Taiwan .
J Med Food. 2013 Sep;16(9):778-84. doi: 10.1089/jmf.2012.2534. Epub 2013 Aug 3.
Silymarin is an active principle from the seeds of the milk thistle plant and is widely used as a hepatoprotective gent due to its antioxidant-like activity. In the present study, we evaluated the potential efficacy of silymarin against oral cancer and investigated its possible mechanism of action. Cell viability assay and western blotting analyses were used to identify silymarin-induced apoptotic cell death in human pharynx squamous cell carcinoma (FaDu) cells. The short interfering RNA (siRNA) is used to confirm the role of phosphatase and tensin homolog (PTEN) in silymarin-induced apoptosis. Treatment of FaDu cells with silymarin resulted in a significant decrease in cell viability (up to 70%). Silymarin inhibited the phosphorylation of Akt (over 10-fold) with an increase in expression of PTEN (five to sixfold). Consequently, the level of Bcl-2 expression was decreased five to sixfold and caspase 3 activated to induce apoptosis. Treatment with siRNA specific to PTEN gene diminished the action of silymarin. The results suggest that silymarin inhibits the Akt signaling pathway by increasing PTEN expression in FaDu cells and directly affects Bcl-2 family members. Also, we demonstrated the inhibitory activity of silymarin for oral cancer is related to cell survival. These mechanisms may in part explain the actions of silymarin and provide a rationale for the development of silymarin as an anticancer agent.
水飞蓟素是奶蓟草种子中的一种活性成分，由于其抗氧化样活性，被广泛用作护肝剂。在本研究中，我们评估了水飞蓟素对口腔癌的潜在疗效，并研究了其可能的作用机制。细胞活力测定和 Western blot 分析用于鉴定水飞蓟素诱导人咽鳞癌细胞（FaDu）凋亡的作用。采用短发夹 RNA（siRNA）确认磷酸酶和张力蛋白同源物（PTEN）在水飞蓟素诱导凋亡中的作用。水飞蓟素处理 FaDu 细胞可显著降低细胞活力（高达 70%）。水飞蓟素抑制 Akt 的磷酸化（超过 10 倍），同时增加 PTEN 的表达（5-6 倍）。结果，Bcl-2 表达水平降低 5-6 倍，caspase 3 激活诱导凋亡。用针对 PTEN 基因的 siRNA 处理可减弱水飞蓟素的作用。结果表明，水飞蓟素通过增加 FaDu 细胞中 PTEN 的表达抑制 Akt 信号通路，并直接影响 Bcl-2 家族成员。此外，我们证明了水飞蓟素对口腔癌的抑制活性与细胞存活有关。这些机制可能部分解释了水飞蓟素的作用，并为将水飞蓟素开发为抗癌剂提供了依据。
