Madan Esha, Prasad Sahdeo, Roy Preeti, George Jasmine, Shukla Yogeshwer
Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow, UP 226001, India.
Biochem Biophys Res Commun. 2008 Dec 26;377(4):1232-7. doi: 10.1016/j.bbrc.2008.10.158. Epub 2008 Nov 6.
Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin present mainly in grapes, red wine and berries, is known to possess strong chemopreventive and anticancer properties. Here, we demonstrated the anti-proliferative and apoptosis-inducing activities of resveratrol in human epidermoid carcinoma A431 cells. Resveratrol has cytotoxic effects through inhibiting cellular proliferation of A431 cells, which leads to the induction of apoptosis, as evident by an increase in the fraction of cells in the sub-G(1) phase of the cell cycle and Annexin-V binding of externalized phosphatidylserine. Results revealed that inhibition of proliferation is associated with regulation of the JAK/STAT pathway, where resveratrol prevents phosphorylation of JAK, thereby inhibiting STAT1 phosphorylation. Furthermore, resveratrol treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. Consequently, an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and subsequent cleavage of PARP, thereby shifting the balance in favor of apoptosis. These observations indicate that resveratrol treatment inhibits JAK/STAT-mediated gene transcription and induce the mitochondrial cell death pathway.
白藜芦醇（反式-3,4',5-三羟基芪）是一种主要存在于葡萄、红酒和浆果中的多酚类植物抗毒素，已知具有强大的化学预防和抗癌特性。在此，我们证明了白藜芦醇在人表皮样癌A431细胞中的抗增殖和诱导凋亡活性。白藜芦醇通过抑制A431细胞的细胞增殖而具有细胞毒性作用，这导致凋亡的诱导，细胞周期亚G(1)期细胞比例增加以及膜联蛋白-V与外化磷脂酰丝氨酸结合可证明这一点。结果显示，增殖的抑制与JAK/STAT信号通路的调节有关，白藜芦醇可阻止JAK的磷酸化，从而抑制STAT1的磷酸化。此外，白藜芦醇处理可积极刺激活性氧（ROS）和线粒体膜去极化。因此，Bax/Bcl-2比例失衡触发了半胱天冬酶级联反应及随后PARP的裂解，从而使平衡向有利于凋亡的方向转变。这些观察结果表明，白藜芦醇处理可抑制JAK/STAT介导的基因转录并诱导线粒体细胞死亡途径。
