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Article Open Access

Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK

  • Authors:
    • Jun Beom Park
    • Jin Sun Lee
    • Myung Sun Lee
    • Eun Young Cha
    • Soyeon Kim
    • Ji Young Sul
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Chungnam National University Hospital, Daejeon 35015, Republic of Korea, Biomedical Research Institute, Chungnam National University Hospital, Daejeon 35015, Republic of Korea
    Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2880-2888
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    Published online on: July 3, 2018
       https://doi.org/10.3892/mmr.2018.9244
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Abstract

5‑Fluorouracil (5‑FU) is one of the most commonly used chemotherapeutic agents for gastric cancer. Resistance to 5‑FU‑based chemotherapy remains the major obstacle in the treatment of gastric cancer. A growing body of evidence has suggested that adenosine monophosphate‑activated protein kinase (AMPK) is pivotal for chemoresistance. However, the mechanism by which AMPK regulates the chemosensitivity of gastric cancer remains unclear. In the present study, how corosolic acid enhanced the chemosensitivity of gastric cancer cells to 5‑FU via AMPK activation was investigated. A 5‑FU‑resistant gastric cancer cell line (SNU‑620/5‑FUR) was established, which had a marked increase in thymidine synthase (TS) expression but reduced AMPK phosphorylation when compared with the parental cell line, SNU‑620. AMPK regulation by 5‑aminoimidazole‑4‑carboxamide ribonucleotide or compound c was revealed to be markedly associated with TS expression and 5‑FU‑resistant cell viability. In addition, corosolic acid activated AMPK, and decreased TS expression and the phosphorylation of mammalian target of rapamycin/4E‑binding protein 1 in a dose‑dependent manner. Corosolic acid treatment significantly reduced cell viability while compound c reversed corosolic acid‑induced cell growth inhibition. The 5‑FU‑resistance sensitization effect of corosolic acid was determined by the synergistic reduction of TS expression and inhibition of cell viability in the presence of 5‑FU. The corosolic acid‑induced AMPK activation was markedly increased by additional 5‑FU treatment, while compound c reversed AMPK phosphorylation. In addition, compound c treatment reversed corosolic acid‑induced apoptotic markers such as capase‑3 and PARP cleavage, and cytochrome c translocation to cytosol, in the presence of 5‑FU. Corosolic acid treatment in the presence of 5‑FU induced an increase in the apoptotic cell population based on flow cytometry analysis. This increase was abolished by compound c. In conclusion, these results implied that corosolic acid may have therapeutic potential to sensitize the resistance of gastric cancer to 5‑FU by activating AMPK.
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Copy and paste a formatted citation
Spandidos Publications style
Park JB, Lee JS, Lee MS, Cha EY, Kim S and Sul JY: Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK. Mol Med Rep 18: 2880-2888, 2018.
APA
Park, J.B., Lee, J.S., Lee, M.S., Cha, E.Y., Kim, S., & Sul, J.Y. (2018). Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK. Molecular Medicine Reports, 18, 2880-2888. https://doi.org/10.3892/mmr.2018.9244
MLA
Park, J. B., Lee, J. S., Lee, M. S., Cha, E. Y., Kim, S., Sul, J. Y."Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK". Molecular Medicine Reports 18.3 (2018): 2880-2888.
Chicago
Park, J. B., Lee, J. S., Lee, M. S., Cha, E. Y., Kim, S., Sul, J. Y."Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK". Molecular Medicine Reports 18, no. 3 (2018): 2880-2888. https://doi.org/10.3892/mmr.2018.9244
Copy and paste a formatted citation
x
Spandidos Publications style
Park JB, Lee JS, Lee MS, Cha EY, Kim S and Sul JY: Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK. Mol Med Rep 18: 2880-2888, 2018.
APA
Park, J.B., Lee, J.S., Lee, M.S., Cha, E.Y., Kim, S., & Sul, J.Y. (2018). Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK. Molecular Medicine Reports, 18, 2880-2888. https://doi.org/10.3892/mmr.2018.9244
MLA
Park, J. B., Lee, J. S., Lee, M. S., Cha, E. Y., Kim, S., Sul, J. Y."Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK". Molecular Medicine Reports 18.3 (2018): 2880-2888.
Chicago
Park, J. B., Lee, J. S., Lee, M. S., Cha, E. Y., Kim, S., Sul, J. Y."Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK". Molecular Medicine Reports 18, no. 3 (2018): 2880-2888. https://doi.org/10.3892/mmr.2018.9244
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