Effects and mechanisms of novel chalcone analogue-A59 on inducing colon cancer cells’ apoptosis
1.Department of Gastroenterological Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015; 2.Department of Gastrointestinal Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015
SUN Yusheng1,ZHU Guanbao2,JIN Jinji2, et al. Effects and mechanisms of novel chalcone analogue-A59 on inducing colon cancer cells’ apoptosis[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2015, 45(6): 421-.
Abstract：Objective: To further explore its anti-tumor activity and mechanisms through investigation of the signal path of novel chalcone analogue-A59. Methods: Synthesize the chalcone analogues and further test their cytotoxicity on colon cancer cell line (HCT-116) through MTT method, and pick out the one own better biological activity named A59. The ability of A59 on inducing HCT-116’s apoptosis and inhibiting its cell cycle were assayed using FCM method. The effect of A59 on ATF4 and CHOP expression in HCT-116 were assayed with Western blot. After knockdown CHOP by siRNA technology, the influence of A59 on cell’s apoptosis through immunofluorescence (IF) and FCM was further investigated. Results: A59 showed inhibitory effects on the proliferation of HCT-116 (IC50=7.6 μm). This novel chalcone analogue exerted its biological activity to induce HCT-116’s apoptosis and inhibit its cell cycle through FCM testing, and the Western blot assay indicated that A59 showed a dose-dependent activation of key protein CHOP of endocytoplasmic reticulum stress (ERS) signal path. and the siRNA technology further confirmed A59 induce apoptosis by stimulating the CHOP over-expression. Conclusion: Novel chalcone analogue-A59 shows inhibitory effects on the proliferation of HCT-116 by activating the ERS signal path’s key protein CHOP. Clarifies its mechanisms and shows the significance on the new anti-colon cancer drug research and development.
