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

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

doi:10.3892/mmr.2016.5818

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

Authors:
- Lin Yang
- Yanqing Liu
- Mei Wang
- Yayun Qian
- Xiaoyun Dong
- Hao Gu
- Haibo Wang
- Shiyu Guo
- Tadashi Hisamitsu
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Affiliations: 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
Published online on: October 10, 2016 https://doi.org/10.3892/mmr.2016.5818
Pages: 4559-4566
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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