Masood Muqaddas, Rasul Azhar, Sarfraz Iqra, Jabeen Faiza, Liu Sitong, Liu Xintong, Wei Wei, Li Jiang, Li Xiaomeng
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
Department of Zoology, Faculty of Science and Technology, Government College University Faisalabad (GCUF), Pakistan/RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
Pak J Pharm Sci. 2019 Sep;32(5(Supplementary)):2237-2243.
Hispolon, a bioactive polyphenolic entity extracted from Phellinus linteus, possesses anticancer, antiinflammatory and anti-oxidant properties. Despite the reported therapeutic effects of this natural chemical entity, inhibitory potential of hispolon towards prostate carcinoma DU145 cells and mechanism of its action are yet to be explicated. Deregulated STAT3 pathway performs multifaceted functions in facilitating the development of cancer. Here, we have investigated the mechanism of hispolon by which it exerts its anticancer effects in DU145 cells and whether its anticancer activity is mediated by modulation of STAT3. Our outcomes show that hispolon significantly halted the multiplication of DU145 cells as well as arrested cell cycle at S phase. S phase arrest induced by hispolon was associated with downregulation of cyclin B1, cyclin D1 and CDK4 while up-regulation of p21. Moreover, hispolon treatment leads towards induction of apoptosis in a dose-dependent mode in DU145 cells. Hispolon induced modulation of Bcl-2 family proteins lead towards loss of MMP allowing the discharge of cytochrome c from mitochondrial porin channels which triggered the cascade of caspases ultimately causing cellular death. We further investigated the role of hispolon in mediating deregulated STAT3 pathways in DU145 cells. Hispolon has potential to downregulate the p-STAT3 expression with no effect on total STAT3. Contemporaneously, these results represent that hispolon's anticancer mechanism of action proceeds via downregulating the phosphorylation of STAT3 and induction of apoptosis via mitochondrial pathway.
桑黄多糖是从桑黄中提取的一种具有生物活性的多酚类物质，具有抗癌、抗炎和抗氧化特性。尽管已有报道称这种天然化学物质具有治疗作用，但其对前列腺癌DU145细胞的抑制潜力及其作用机制仍有待阐明。失调的信号转导和转录激活因子3（STAT3）通路在促进癌症发展中发挥多方面作用。在此，我们研究了桑黄多糖在DU145细胞中发挥抗癌作用的机制，以及其抗癌活性是否通过调节STAT3介导。我们的结果表明，桑黄多糖显著抑制DU145细胞的增殖，并使细胞周期停滞于S期。桑黄多糖诱导的S期停滞与细胞周期蛋白B1、细胞周期蛋白D1和细胞周期蛋白依赖性激酶4（CDK4）的下调以及p21的上调有关。此外，桑黄多糖处理以剂量依赖方式诱导DU145细胞凋亡。桑黄多糖诱导的Bcl-2家族蛋白调节导致线粒体膜电位丧失，使细胞色素c从线粒体孔蛋白通道释放，从而触发半胱天冬酶级联反应，最终导致细胞死亡。我们进一步研究了桑黄多糖在介导DU145细胞中失调的STAT3通路中的作用。桑黄多糖有下调磷酸化STAT3表达的潜力，而对总STAT3无影响。同时，这些结果表明桑黄多糖的抗癌作用机制是通过下调STAT3的磷酸化并通过线粒体途径诱导凋亡来实现的。
