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

• Published in: Molecular medicine reports Vol. 14; no. 5; pp. 4559 - 4566
• Main Authors: Yang, Lin, Liu, Yanqing, Wang, Mei, Qian, Yayun, Dong, Xiaoyun, Gu, Hao, Wang, Haibo, Guo, Shiyu, Hisamitsu, Tadashi
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.11.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: 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; United States > US
• ISSN: 1791-2997; 1791-3004; 1791-3004
• DOI: 10.3892/mmr.2016.5818

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.