title: Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis.
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.
authors.affiliation: Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Dong
authors.affiliation: Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gu
authors.affiliation: Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo 142‑8555, Japan.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo 142‑8555, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hisamitsu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D000075686:COP9 Signalosome Complex; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D011794:Quercetin / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C470634:COPS6 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D011794:Quercetin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D000075686:COP9 Signalosome Complex