Journal Article

Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis

Dong, Xiaoyun, Yang, Lin, Hisamitsu, Tadashi, Wang, Haibo, Gu, Hao, Wang, Mei, Liu, Yanqing, Guo, Shiyu, Qian, Yayun

2016

Overview

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.

• Publisher: D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
• Subject: Adaptor Proteins, Signal Transducing - biosynthesis / Adaptor Proteins, Signal Transducing - genetics / AKT protein / Apoptosis / Apoptosis - drug effects / B-cell lymphoma / Bcl-2 protein / Bcl-x protein / Carcinogenesis / Carcinogenesis - drug effects / Carcinogenesis - genetics / Care and treatment / Cell cycle / Cell Proliferation - drug effects / Cellular signal transduction / Chromatin / Colon cancer / Colonic Neoplasms - drug therapy / Colonic Neoplasms - genetics / Colonic Neoplasms - pathology / Colorectal cancer / Colorectal carcinoma / COP9 Signalosome Complex / CSN6 / Development and progression / Dose-Response Relationship, Drug / Electron microscopy / Flow cytometry / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Health aspects / HT-29 colon cancer cells / HT29 Cells / Humans / Kinases / Leukemia / Lymphocytes B / Lymphoma / Mammalian cells / MDM2 protein / Myc / Myc protein / p53 Protein / Phosphorylation / Photomorphogenesis / Protein expression / Proteins / Proto-Oncogene Proteins c-akt - biosynthesis / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-myc - biosynthesis / Proto-Oncogene Proteins c-myc - genetics / Quercetin / Quercetin - administration & dosage / Signal Transduction - drug effects / Studies / Transmission electron microscopy / Western blotting