Department of Pharmacy, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China; Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, 400016, China.
Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, 400016, China.
Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):197-204. doi: 10.1016/j.bbrc.2022.10.077. Epub 2022 Oct 25.
High malignancy and mortality in colon cancer require clarifying the underlying mechanisms of colon cancer carcinogenesis and exploring new targets or drugs for the clinical treatment of colon cancer. Resveratrol (Res), a natural compound, shows cytotoxicity against various tumors. However, the specific anti-cancer mechanism of Res remains unclear. In the present study, we aimed to explore the anti-cancer activity of Res against colon cancer cells and the possible mechanism. The results showed that Res could inhibit cell proliferation and induce cell cycle arrest and apoptosis in HCT116 cells. Western blotting and Polymerase chain reaction (PCR) showed that Res increased the phosphorylated YAP (pYAP) levels and decreased YAP total protein level and decreased the mRNA expression of the YAP signaling downstream genes CTGF and CYR61. The effects of Res on pYAP were enhanced by YAP inhibitor verteporfin (VP). VP also enhanced the effects of Res on decreasing viability and inducing apoptosis. Furthermore, the molecular docking analysis indicated Res could bind with YAP-TEAD through van der Waals, pi-alkyl, and pi-pi stacked interactions. Our findings suggested that the anti-cancer activity of Res may be mediated via activating Hippo/YAP signaling and partially disturbing the interaction between YAP and TEAD. All this evidence supports that Res may be an efficacious drug for colon cancer treatment.
结直肠癌恶性程度高、死亡率高，阐明其发病机制，探索新的靶点或药物对结直肠癌的临床治疗具有重要意义。白藜芦醇（Res）是一种天然化合物，对多种肿瘤具有细胞毒性。然而，Res 的具体抗癌机制尚不清楚。本研究旨在探讨 Res 对结肠癌细胞的抗癌活性及其可能的机制。结果表明，Res 可抑制 HCT116 细胞的增殖，并诱导细胞周期停滞和凋亡。Western blot 和聚合酶链反应（PCR）结果显示，Res 增加了磷酸化 YAP（pYAP）水平，降低了 YAP 总蛋白水平，并降低了 YAP 信号下游基因 CTGF 和 CYR61 的 mRNA 表达。YAP 抑制剂 verteporfin（VP）增强了 Res 对 pYAP 的作用。VP 还增强了 Res 降低活力和诱导细胞凋亡的作用。此外，分子对接分析表明 Res 可通过范德华力、π-烷基和π-π堆积相互作用与 YAP-TEAD 结合。我们的研究结果表明，Res 的抗癌活性可能是通过激活 Hippo/YAP 信号通路，部分干扰 YAP 与 TEAD 的相互作用来介导的。所有这些证据都支持 Res 可能是一种有效的结直肠癌治疗药物。
