Imai-Sumida Mitsuho, Chiyomaru Takeshi, Majid Shahana, Saini Sharanjot, Nip Hannah, Dahiya Rajvir, Tanaka Yuichiro, Yamamura Soichiro
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA, USA.
Current address: Department of Urology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan.
Oncotarget. 2017 Sep 8;8(54):92032-92042. doi: 10.18632/oncotarget.20734. eCollection 2017 Nov 3.
Silibinin is the major active constituent of silymarin, an extract of milk thistle seeds. Silibinin has been shown to have significant anti-cancer effects in a variety of malignancies. However, the molecular mechanisms of silibinin action in bladder cancer have not been studied extensively. In the present study, we found that silibinin (10 μM) significantly suppressed proliferation, migration, invasion and induced apoptosis of T24 and UM-UC-3 human bladder cancer cells. Silibinin down-regulated the actin cytoskeleton and phosphatidylinositide 3-kinase (PI3K)/Akt signaling pathways in these cancer cell lines. These pathways were found to crosstalk through RAS cascades. We found that silibinin suppressed levels of trimethylated histone H3 lysine 4 and acetylated H3 at the promoter. Furthermore, silibinin targets long non-coding RNA: HOTAIR and ZFAS1, which are known to play roles as oncogenic factors in various cancers. This study shows that silibinin exerts anti-cancer effects through down-regulation of actin cytoskeleton and PI3K/Akt pathways and thus suppresses bladder cancer growth and progression.
水飞蓟宾是水飞蓟素的主要活性成分，水飞蓟素是一种从水飞蓟种子中提取的物质。水飞蓟宾已被证明在多种恶性肿瘤中具有显著的抗癌作用。然而，水飞蓟宾在膀胱癌中的作用分子机制尚未得到广泛研究。在本研究中，我们发现水飞蓟宾（10 μM）显著抑制T24和UM-UC-3人膀胱癌细胞的增殖、迁移、侵袭并诱导其凋亡。水飞蓟宾下调了这些癌细胞系中的肌动蛋白细胞骨架和磷脂酰肌醇3激酶（PI3K）/Akt信号通路。发现这些通路通过RAS级联相互作用。我们发现水飞蓟宾抑制了启动子处三甲基化组蛋白H3赖氨酸4和乙酰化H3的水平。此外，水飞蓟宾靶向长链非编码RNA：HOTAIR和ZFAS1，已知它们在各种癌症中作为致癌因子发挥作用。本研究表明，水飞蓟宾通过下调肌动蛋白细胞骨架和PI3K/Akt通路发挥抗癌作用，从而抑制膀胱癌的生长和进展。
