Yang Lin, Liu Yanqing, Wang Mei, Qian Yayun, Dong Xiaoyun, Gu Hao, Wang Haibo, Guo Shiyu, Hisamitsu Tadashi
Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
Department of Physiology, School of Medicine, Showa University, Tokyo 142‑8555, Japan.
Mol Med Rep. 2016 Nov;14(5):4559-4566. doi: 10.3892/mmr.2016.5818. Epub 2016 Oct 10.
Constitutive photomorphogenesis 9 signalosome (CSN) consists of a total of eight subunits (CSN1-CSN8) in mammalian cells. CSN6 may promote carcinogenesis by positively regulating v‑myc avian myelocytomatosis viral oncogene homolog (Myc) and MDM2 proto‑oncogene stability, and is regarded as a potential target for cancer therapy. Quercetin has a substantial anticancer effect on various human cancer cells. The present study investigated the effects of quercetin on HT-29 human colorectal cancer cell viability, apoptosis and cell cycle arrest using an MTT assay, flow cytometry, transmission electron microscopy and western blotting. It was determined that quercetin inhibited HT‑29 cell viability in a dose‑dependent manner. Cell shrinkage, chromatin condensation and nuclear collapse were observed in the 50, 100 and 200 µM quercetin groups. The exposure of HT‑29 cells to quercetin led to significant cell cycle arrest in the S‑phase. Western blot analysis revealed that quercetin reduced the protein expression levels of phosphorylated-Akt and increased CSN6 protein degradation; therefore, affecting the expression levels of Myc, p53, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2 associated X protein. The overexpression of CSN6 reduced the effect of quercetin treatment on HT‑29 cells, suggesting that quercetin‑induced apoptosis may involve the Akt‑CSN6‑Myc signaling axis in HT‑29 cells.
组成型光形态建成9信号体（CSN）在哺乳动物细胞中总共由八个亚基（CSN1 - CSN8）组成。CSN6可能通过正向调节v - myc禽骨髓细胞瘤病毒癌基因同源物（Myc）和MDM2原癌基因的稳定性来促进肿瘤发生，并且被视为癌症治疗的潜在靶点。槲皮素对多种人类癌细胞具有显著的抗癌作用。本研究使用MTT法、流式细胞术、透射电子显微镜和蛋白质印迹法研究了槲皮素对HT - 29人结肠癌细胞活力、凋亡和细胞周期阻滞的影响。结果确定槲皮素以剂量依赖性方式抑制HT - 29细胞活力。在50、100和200μM槲皮素组中观察到细胞皱缩、染色质浓缩和核固缩。HT - 29细胞暴露于槲皮素导致S期明显的细胞周期阻滞。蛋白质印迹分析显示，槲皮素降低了磷酸化Akt的蛋白质表达水平并增加了CSN6蛋白质降解；因此，影响了Myc、p53、B细胞淋巴瘤2（Bcl - 2）和Bcl - 2相关X蛋白的表达水平。CSN6的过表达降低了槲皮素处理对HT - 29细胞的作用，表明槲皮素诱导的凋亡可能涉及HT - 29细胞中的Akt - CSN6 - Myc信号轴。
