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Oleic acid and oleoylethanolamide decrease interferon-γ-induced expression of PD-L1 and induce apoptosis in human

Kazuo Yamagata1, Erika Uzu1, Yuri Yoshigai1

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Oleic acid and its metabolite, oleoylethanolamide (OEA), were found to inhibit programmed death-ligand 1 (PD-L1) expression in cancer cells. These compounds may prevent cancer by inducing apoptosis through STAT phosphorylation.

Keywords:
ApoptosisInterferon-γLung cancerOleic acidPD-L1

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Programmed death-ligand 1 (PD-L1) inhibition is a strategy to prevent cancer progression.
  • Oleic acid exhibits anti-cancer properties, but its effect on PD-L1 is unproven.

Purpose of the Study:

  • To investigate the effects of oleic acid and oleoylethanolamide (OEA) on PD-L1 expression and tumorigenesis biomarkers.
  • To explore the potential of these compounds in cancer prevention.

Main Methods:

  • Utilized RT-PCR to analyze PD-L1 and apoptosis-related gene expression in A549, HuH-7, MCF-7, DLD-1, and LoVo cancer cell lines.
  • Employed western blotting to assess Interferon-gamma (IFN-γ)-induced PD-L1 protein modulation.
  • Examined the impact on STAT phosphorylation.

Main Results:

  • IFN-γ stimulation increased PD-L1 expression across tested cancer cell lines, notably in A549 cells.
  • Oleic acid and OEA reduced IFN-γ-induced PD-L1, Bax, Bcl-2, and caspase 3 expression in A549 cells.
  • Both compounds decreased IFN-γ-induced STAT phosphorylation.

Conclusions:

  • Oleic acid and OEA inhibit PD-L1 expression and promote apoptosis via STAT phosphorylation.
  • These findings suggest oleic acid and OEA may prevent cancer formation by modulating the STAT pathway.
  • Results offer new insights into the anti-cancer potential of oleic acid-rich oils like olive oil.