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Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system in vitro

  • Authors:
    • Mariko Kogami
    • Shinji Abe
    • Hiroyuki Nakamura
    • Kazutetsu Aoshiba
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki 300‑0395, Japan, Department of Respiratory Medicine, Tokyo Medical University, Tokyo 160‑0023, Japan, Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki 300‑0395, Japan
    Copyright: © Kogami et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 313
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    Published online on: June 6, 2023
       https://doi.org/10.3892/ol.2023.13899
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Abstract

Fenofibrate (FF) is a peroxisome proliferator‑ activated receptor (PPAR)‑α agonist that is widely used for the treatment of hyperlipidemia. It has been shown to have pleiotropic actions beyond its hypolipidemic effect. FF has been shown to exert a cytotoxic effect on some cancer cells when used at higher than clinically relevant concentrations; on the other hand, its cytoprotective effect on normal cells has also been reported. The present study assessed the effect of FF on cisplatin (CDDP) cytotoxicity to lung cancer cells in vitro. The results demonstrated that the effect of FF on lung cancer cells depends on its concentration. FF at ≤50 µM, which is a clinically achievable blood concentration, attenuated CDDP cytotoxicity to lung cancer cells, whereas FF at ≥100 µM, albeit clinically unachievable, had an anticancer effect. The mechanism of FF attenuation of CDDP cytotoxicity involved PPAR‑α‑dependent aryl hydrocarbon receptor (AhR) expression, which in turn stimulated nuclear factor erythroid 2‑related factor 2 (Nrf2) expression and antioxidant production, resulting in lung cancer cell protection from CDDP‑evoked oxidative damage. In conclusion, the present study revealed that FF, at clinically relevant concentrations, attenuated CDDP cytotoxicity to lung cancer cells by enhancing the antioxidant defense system through activation of a pathway that involves the PPAR‑α‑PPAR response element‑AhR xenobiotic response element‑Nrf2‑antioxidant response element. These findings suggested that concomitant use of FF with CDDP may compromise the efficacy of chemotherapy. Although the anticancer property of FF has recently attracted much attention, concentrations that exceed clinically relevant concentrations are required.
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Copy and paste a formatted citation
Spandidos Publications style
Kogami M, Abe S, Nakamura H and Aoshiba K: Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>. Oncol Lett 26: 313, 2023.
APA
Kogami, M., Abe, S., Nakamura, H., & Aoshiba, K. (2023). Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>. Oncology Letters, 26, 313. https://doi.org/10.3892/ol.2023.13899
MLA
Kogami, M., Abe, S., Nakamura, H., Aoshiba, K."Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>". Oncology Letters 26.1 (2023): 313.
Chicago
Kogami, M., Abe, S., Nakamura, H., Aoshiba, K."Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>". Oncology Letters 26, no. 1 (2023): 313. https://doi.org/10.3892/ol.2023.13899
Copy and paste a formatted citation
x
Spandidos Publications style
Kogami M, Abe S, Nakamura H and Aoshiba K: Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>. Oncol Lett 26: 313, 2023.
APA
Kogami, M., Abe, S., Nakamura, H., & Aoshiba, K. (2023). Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>. Oncology Letters, 26, 313. https://doi.org/10.3892/ol.2023.13899
MLA
Kogami, M., Abe, S., Nakamura, H., Aoshiba, K."Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>". Oncology Letters 26.1 (2023): 313.
Chicago
Kogami, M., Abe, S., Nakamura, H., Aoshiba, K."Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system <em>in vitro</em>". Oncology Letters 26, no. 1 (2023): 313. https://doi.org/10.3892/ol.2023.13899
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