title: The PTEN/PI3K/Akt and Wnt/β-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation.
abstract: Colon cancer is one of the most common malignancies and the treatments for colon cancer have been developed substantially in the last decades, but there is still a great clinical need to explore new treatment regimens due to the undesirable prognosis. In this investigation, we demonstrated the anti-proliferative and apoptosis-inducing activities of resveratrol (Res) in human colon cancer cells, and the possible mechanisms underlying these effects. We used crystal violet staining, flow cytometry and western blotting to validate the anti-proliferative and apoptosis-inducing effects of Res on HCT116 cells. A xenograft tumor model was used to confirm the anti-proliferative effects of Res. We employed polymerase chain reaction, western blotting, recombinant adenovirus and luciferase reporter assay to explore the possible mechanism(s) of action. We found that Res inhibits significantly the proliferation and promotes apoptosis in HCT116 cells, as well as inhibits the xenograft tumor growth of colon cancer. Res upregulates the expression of phosphatase and tensin homolog (PTEN) and decreases the phosphorylation of Akt1/2. The exogenous expression of PTEN inhibits the PI3K/Akt signal and promotes the anti-proliferative effects of Res in HCT116 cells, while knockdown of PTEN increases PI3K/Akt signal but reduces the anti-proliferative function of Res. The protein and mRNA expression of β-catenin are all decreased by Res concentration-dependently. Thus, our findings strongly suggest that the anti-proliferative effects of Res in human colon cancer cells may be mediated by regulating separately the PTEN/PI3K/Akt and Wnt/β-catenin signaling.
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Meng
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Shuang-Xue
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Key Laboratory for Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Luo
authors.affiliation: Key Laboratory for Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Zuo
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yin
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Deng
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Jun-Qin
authors.initials: JQ
authors.lastname: Yang
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Sun
authors.affiliation: Chongqing Municipal Key Laboratory of Higher Education Institutions for Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000077185:Resveratrol