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Sulforaphane Induces Colorectal Cancer Cell Proliferation through Nrf2 Activation in a p53‐Dependent Manner
Author(s) -
Oh Jisun,
Kim JongSang
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb336
Subject(s) - sulforaphane , apoptosis , cell growth , chemistry , cancer research , cancer cell , microbiology and biotechnology , biology , cancer , biochemistry , genetics
Sulforaphane is a well‐known phytochemical that stimulates nuclear factor erythroid 2‐related factor 2 (Nrf2)‐mediated expression of antioxidant and detoxifying enzymes. In this study, we found that sulforaphane promotes cell proliferation in HCT116 human colon cancer cells harboring a normal p53 gene in a dose‐dependent but biphasic manner. Since p53 has been reported to contribute to cell survival by regulating various metabolic pathways to adapt to mild stress, we further examined cellular responses in both p53‐wild‐type (WT) and p53‐knockout (KO) HCT116 cells exposed to sulforaphane in vitro and in vivo . Results demonstrated that sulforaphane treatment (i) activated Nrf2‐mediated antioxidant enzymes in both p53‐WT and p53‐KO cells, (ii) decreased apoptotic protein expression in WT cells but increased in KO cells in a dose‐dependent manner, (iii) marginally changed mitochondrial DNA abundance in WT cells but decreased in KO cells, and (iv) increased the expression of a mitochondrial biogenesis marker PGC1α in WT cells but decreased in KO cells. Moreover, a low dose of sulforaphane promoted tumor growth, upregulated the Nrf2 signaling pathway, and decreased apoptotic cell death in p53‐WT HCT116 xenografts compared to that in p53‐KO HCT116 xenografts in BALB/c nude mice. These findings suggest that sulforaphane can influence colon cancer cell proliferation and mitochondrial function through a crosstalk between the Nrf2 signaling pathway and p53 axis. Support or Funding Information This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT), Republic of Korea (Grant No. 2017R1A2B4005087). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .