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Article

Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation

  • Authors:
    • Mingming Cao
    • Zhuoran Zhang
    • Su Han
    • Xi Lu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Pharmacy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Parasitology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
  • Pages: 3941-3947
    |
    Published online on: March 1, 2019
       https://doi.org/10.3892/mmr.2019.10002
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Abstract

Butyrate, a histone deacetylase inhibitor, is a typical short chain fatty acid produced by gut microbiota, the dysmetabolism of which has been consistently associated with colorectal diseases. However, its role in tumorigenesis and progression of colorectal cancer cells remains under‑investigated. The present study examined the antitumor function of butyrate in the colorectal cancer cell line HCT116 and investigated the underlying molecular mechanism. MTT assay was used to measure cell proliferation and ELISA assay was used to determine cell apoptosis by measuring histone release and caspase‑3 activation. The results demonstrated that butyrate treatment significantly inhibited proliferation and induced apoptosis in HCT116 cells with an increased B‑cell lymphoma-2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio. Western blotting demonstrated that the phosphorylation of mammalian target of rapamycin (mTOR) at Ser2448, ribosomal protein S6 kinase β‑1 (S6K1) at Thr389, S6 at Ser235/236 and expression of silent mating type information regulation 2 homolog (SIRT)1 were decreased following butyrate treatment, while the acetylation of S6K1 was indicated to be increased. Silencing of SIRT1 by small interfering RNA technology demonstrated a similar inhibition on growth, induction of apoptosis, elevation of S6K1 acetylation and deactivation of mTOR/S6K1 signaling. Butyrate treatment also enhanced the inhibition of SIRT1 silencing on cell proliferation and activity of mTOR/S6K1. The activation of mTOR/S6K1 signaling and upregulation of cell proliferation mediated by overexpression of SIRT1 were blocked by butyrate. These data suggested that butyrate inhibited proliferation and induced apoptosis in HCT116 cells by deactivating mTOR/S6K1 signaling, possibly through its inhibition of SIRT1.
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Copy and paste a formatted citation
Spandidos Publications style
Cao M, Zhang Z, Han S and Lu X: Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation. Mol Med Rep 19: 3941-3947, 2019.
APA
Cao, M., Zhang, Z., Han, S., & Lu, X. (2019). Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation. Molecular Medicine Reports, 19, 3941-3947. https://doi.org/10.3892/mmr.2019.10002
MLA
Cao, M., Zhang, Z., Han, S., Lu, X."Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation". Molecular Medicine Reports 19.5 (2019): 3941-3947.
Chicago
Cao, M., Zhang, Z., Han, S., Lu, X."Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation". Molecular Medicine Reports 19, no. 5 (2019): 3941-3947. https://doi.org/10.3892/mmr.2019.10002
Copy and paste a formatted citation
x
Spandidos Publications style
Cao M, Zhang Z, Han S and Lu X: Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation. Mol Med Rep 19: 3941-3947, 2019.
APA
Cao, M., Zhang, Z., Han, S., & Lu, X. (2019). Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation. Molecular Medicine Reports, 19, 3941-3947. https://doi.org/10.3892/mmr.2019.10002
MLA
Cao, M., Zhang, Z., Han, S., Lu, X."Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation". Molecular Medicine Reports 19.5 (2019): 3941-3947.
Chicago
Cao, M., Zhang, Z., Han, S., Lu, X."Butyrate inhibits the proliferation and induces the apoptosis of colorectal cancer HCT116 cells via the deactivation of mTOR/S6K1 signaling mediated partly by SIRT1 downregulation". Molecular Medicine Reports 19, no. 5 (2019): 3941-3947. https://doi.org/10.3892/mmr.2019.10002
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