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Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer

  • Authors:
    • Jung-Lim Kim
    • Dae-Hee Lee
    • Cheol-Ho Pan
    • Su Jin Park
    • Sang-Cheul Oh
    • Suk-Young Lee
  • View Affiliations / Copyright

    Affiliations: Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul 08308, Republic of Korea, Department of Marine Food Science and Technology, Gangneung‑Wonju National University, Gangneung, Gangwon 25457, Republic of Korea, Natural Product Informatics Research Center, Korea Institute of Science and Technology Gangneung Institute of Natural Products, Gangneung, Gangwon 25451, Republic of Korea, Department of Surgery, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi 15865, Republic of Korea, Division of Hemato‑Oncology, Department of Internal Medicine, School of Medicine, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi 15865, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 321
    |
    Published online on: July 19, 2022
       https://doi.org/10.3892/ol.2022.13441
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Abstract

Phloretin is one of the apple polyphenols with anticancer activities. Since tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) serves important roles in inducing apoptosis, the present study examined the effect of phloretin on TRAIL‑induced apoptosis in colon cancer cells. Treatment with both phloretin and TRAIL markedly suppressed the survival of cancer cells from several colon cancer cell lines compared with that of cells treated with either TRAIL or phloretin. Additionally, decreased numbers of colonies were observed following addition of phloretin and TRAIL. Furthermore, TRAIL‑ and phloretin‑treated HT‑29‑Luc cells exhibited decreased luciferase activity. Increased apoptosis was observed in phloretin‑ and TRAIL‑treated HT‑29‑Luc colon cancer cells, accompanying elevated levels of cleaved poly(ADP‑ribose) polymerase, and caspase‑3, ‑8 and ‑9. The expression levels of MCL1 apoptosis regulator BCL2 family member (Mcl‑1) were decreased following addition of phloretin in colon cancer cells. In addition, overexpression of Mcl‑1 in phloretin‑ and TRAIL‑treated HT‑29‑Luc cells resulted in increased cell survival. Treatment of HT‑29‑Luc cells with a combination of cycloheximide (CHX) and phloretin led to a more prominent decrease in Mcl‑1 expression compared with that in cells treated with CHX alone, while Mcl‑1 expression was recovered by treatment with MG132. Binding of ubiquitin with Mcl‑1 was verified using immunoprecipitation. Intraperitoneal injection of both TRAIL and phloretin into tumor xenografts was associated with a decreased tumor volume compared with that following injection with either TRAIL or phloretin. Overall, the present results suggest a synergistic effect of phloretin on TRAIL‑induced apoptosis in colon cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Kim J, Lee D, Pan C, Park SJ, Oh S and Lee S: Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer. Oncol Lett 24: 321, 2022.
APA
Kim, J., Lee, D., Pan, C., Park, S.J., Oh, S., & Lee, S. (2022). Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer. Oncology Letters, 24, 321. https://doi.org/10.3892/ol.2022.13441
MLA
Kim, J., Lee, D., Pan, C., Park, S. J., Oh, S., Lee, S."Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer". Oncology Letters 24.3 (2022): 321.
Chicago
Kim, J., Lee, D., Pan, C., Park, S. J., Oh, S., Lee, S."Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer". Oncology Letters 24, no. 3 (2022): 321. https://doi.org/10.3892/ol.2022.13441
Copy and paste a formatted citation
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Spandidos Publications style
Kim J, Lee D, Pan C, Park SJ, Oh S and Lee S: Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer. Oncol Lett 24: 321, 2022.
APA
Kim, J., Lee, D., Pan, C., Park, S.J., Oh, S., & Lee, S. (2022). Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer. Oncology Letters, 24, 321. https://doi.org/10.3892/ol.2022.13441
MLA
Kim, J., Lee, D., Pan, C., Park, S. J., Oh, S., Lee, S."Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer". Oncology Letters 24.3 (2022): 321.
Chicago
Kim, J., Lee, D., Pan, C., Park, S. J., Oh, S., Lee, S."Role of phloretin as a sensitizer to TRAIL‑induced apoptosis in colon cancer". Oncology Letters 24, no. 3 (2022): 321. https://doi.org/10.3892/ol.2022.13441
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