Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis.
Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis.
复制标题
槲皮素通过抑制 Akt-CSN6-Myc 信号轴诱导 HT-29 结肠癌细胞凋亡
DOI：
10.3892/mmr.2016.5818
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发表时间：
2016-11
影响因子：
3.4
通讯作者：
Hisamitsu T
中科院分区：
文献类型：
--
作者：
Yang L;Liu Y;Wang M;Qian Y;Dong X;Gu H;Wang H;Guo S;Hisamitsu T
哺乳动物细胞中组成型光形态建成9信号体（CSN）总共由8个亚基（CSN 1-CSN 8）组成。CSN 6可能通过正向调节v-myc禽骨髓细胞瘤病病毒癌基因同源物（Myc）和MDM 2原癌基因的稳定性而促进肿瘤的发生，被认为是肿瘤治疗的潜在靶点。槲皮素对多种人类癌细胞具有显著的抗癌作用。本研究采用MTT法、流式细胞仪、透射电镜和Western blotting等方法研究槲皮素对HT-29人结直肠癌细胞活力、凋亡和细胞周期阻滞的影响。已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200 µM槲皮素组中观察到细胞收缩、染色质凝聚和核塌陷。HT-29细胞暴露于槲皮素导致显著的细胞周期停滞在S期。Western blot分析表明，槲皮素降低了磷酸化Akt蛋白的表达水平，增加了CSN 6蛋白的降解，从而影响了Myc、p53、B细胞淋巴瘤2（Bcl-2）和Bcl-2相关X蛋白的表达水平。CSN 6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HT-29细胞凋亡可能涉及Akt-CSN 6-Myc信号轴。
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.