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Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation

  • Authors:
    • Qian Hao
    • Min Wang
    • Nuan‑Xin Sun
    • Cheng Zhu
    • Ying‑Min Lin
    • Cui Li
    • Fang Liu
    • Wen‑Wen Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Geriatric Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Jiangxi Medical School, Nanchang University, Nanchang, Jiangxi 330031, P.R. China, Department of General Practice, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong 271000, P.R. China
    Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1067-1080
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    Published online on: February 10, 2020
       https://doi.org/10.3892/or.2020.7495
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Abstract

The long pre‑cancerous state of colorectal cancer (CRC) provides an opportunity to prevent the occurrence and development of CRC. The detoxification of CRC food‑borne carcinogenic heterocyclic amines is highly dependent on UDP glucuronosyltransferase 1A (UGT1A)‑mediated glucuronidation. Sulforaphane (SFN), a phytochemical, possesses antioxidant, anti‑inflammatory and anticarcinogenic effects on the prevention of CRC. Previous studies revealed that SFN upregulates the expression of UGT1A. The aim of the present study was to investigate the regulatory mechanism of SFN‑induced UGT1A upregulation and provide novel understanding on the basic research and chemoprevention of CRC. In the present study, the viability and proliferation of CRC cells (HT‑29 and SW480) treated with SFN were assessed by MTT, colony formation and EdU assays. Flow cytometry was used to detect the cell cycle arrest and apoptosis of cells treated with different concentrations of SFN. The motility of cells was determined by wound healing and Transwell assays. Nuclear factor, erythroid 2 like 2 (Nrf2) short hairpin RNA (shRNA) and negative control shRNA lentiviruses were used for cell transfection. Reverse transcription‑quantitative polymerase chain reaction and western blotting were employed to verify the role of Nrf2 in SFN‑induced UGT1A. HT‑29 and SW480 cells were divided into a control, an SFN and a PD98059 [an extracellular signal‑regulated kinase (ERK) inhibitor] + SFN group. Western blotting detected the protein levels of Nrf2 and UGT1A. Intracellular levels of reactive oxygen species (ROS) were detected using a reactive oxygen assay kit. The results revealed that SFN inhibits cell proliferation and colony formation, promotes apoptosis, and reduces the migratory ability of CRC cells. The phosphorylation of ERK induced by SFN promoted Nrf2 accumulation. Furthermore, a significant increase in the levels of UGT1A was observed, which coincided with SFN‑induced upregulation of Nrf2 levels in nuclear fractions. Pretreatment with PD58059 reversed the SFN‑induced subcellular translocation of Nrf2 and the expression of UGT1A. In addition, SFN‑induced high levels of ROS in CRC cells may be associated with the ERK signaling pathway. Collectively, these results indicated that SFN inhibited the proliferation of CRC cells and upregulated the expression of UGT1A in CRC cells via the ERK/Nrf2 signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Hao Q, Wang M, Sun NX, Zhu C, Lin YM, Li C, Liu F and Zhu WW: Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation. Oncol Rep 43: 1067-1080, 2020.
APA
Hao, Q., Wang, M., Sun, N., Zhu, C., Lin, Y., Li, C. ... Zhu, W. (2020). Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation. Oncology Reports, 43, 1067-1080. https://doi.org/10.3892/or.2020.7495
MLA
Hao, Q., Wang, M., Sun, N., Zhu, C., Lin, Y., Li, C., Liu, F., Zhu, W."Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation". Oncology Reports 43.4 (2020): 1067-1080.
Chicago
Hao, Q., Wang, M., Sun, N., Zhu, C., Lin, Y., Li, C., Liu, F., Zhu, W."Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation". Oncology Reports 43, no. 4 (2020): 1067-1080. https://doi.org/10.3892/or.2020.7495
Copy and paste a formatted citation
x
Spandidos Publications style
Hao Q, Wang M, Sun NX, Zhu C, Lin YM, Li C, Liu F and Zhu WW: Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation. Oncol Rep 43: 1067-1080, 2020.
APA
Hao, Q., Wang, M., Sun, N., Zhu, C., Lin, Y., Li, C. ... Zhu, W. (2020). Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation. Oncology Reports, 43, 1067-1080. https://doi.org/10.3892/or.2020.7495
MLA
Hao, Q., Wang, M., Sun, N., Zhu, C., Lin, Y., Li, C., Liu, F., Zhu, W."Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation". Oncology Reports 43.4 (2020): 1067-1080.
Chicago
Hao, Q., Wang, M., Sun, N., Zhu, C., Lin, Y., Li, C., Liu, F., Zhu, W."Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation". Oncology Reports 43, no. 4 (2020): 1067-1080. https://doi.org/10.3892/or.2020.7495
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