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Anthocyanin Oligomers Induce Apoptosis and Autophagy by Inhibiting the mTOR Signaling Pathway in Human Breast Cancer

Min-Gu Lee1, Hyun-Jin Hong1, Kyung-Soo Nam1

  • 1Department of Pharmacology and Intractable Disease Research Center, School of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea.

Pharmaceuticals (Basel, Switzerland)
|January 23, 2024
PubMed

Insights

Anthocyanin oligomers (AOs) show potent anti-cancer effects by inducing apoptosis and autophagy in breast cancer cells. These grape-derived compounds inhibit key survival pathways, suggesting their potential as a novel breast cancer therapy.

Area of Science:

  • Phytochemistry
  • Molecular Biology
  • Oncology

Background:

  • Anthocyanin oligomers (AOs) are derived from grape skins and exhibit greater biological activity than monomeric anthocyanins.
  • Breast cancer, particularly triple-negative and HER2-overexpressing subtypes, remains a significant health concern requiring novel therapeutic strategies.

Purpose of the Study:

  • To investigate the anti-cancer effects of an anthocyanin oligomer (AO) on MDA-MB-231 and SK-BR-3 breast cancer cells.
  • To elucidate the molecular mechanisms underlying the AO's anti-cancer activity, including its impact on cell viability, DNA damage, apoptosis, autophagy, and key signaling pathways.

Main Methods:

  • Treatment of MDA-MB-231 and SK-BR-3 cells with varying concentrations of AO and delphinidin.
  • Assessment of cell viability using standard assays.
  • Analysis of DNA damage marker (H2A.X phosphorylation) and protein levels of RAD51, survivin, LC3-II, p62, and cleaved PARP1 via Western blotting.
  • Evaluation of apoptosis through caspase-3 activity and PARP1 cleavage.
  • Induction of autophagy by measuring LC3-II puncta and protein levels.
  • Inhibition of signaling pathways including HER2, EGFR1, AKT, and mTOR.

Main Results:

  • AO significantly inhibited cell viability in both breast cancer cell lines in a dose-dependent manner, unlike delphinidin.
  • AO treatment led to increased DNA damage (H2A.X phosphorylation), reduced DNA repair (RAD51), and decreased cell survival (survivin).
  • AO induced apoptosis via caspase-3-dependent PARP1 cleavage and promoted autophagy, evidenced by increased LC3-II puncta and protein levels.
  • AO suppressed the mTOR pathway by inhibiting HER2, EGFR1, and AKT signaling cascades.

Conclusions:

  • Anthocyanin oligomers exert anti-cancer effects by simultaneously inducing apoptosis and autophagy in breast cancer cells.
  • The observed anti-cancer activity is mediated through caspase-3-dependent PARP1 cleavage and mTOR pathway inhibition.
  • Anthocyanin oligomers represent promising candidates for the development of novel breast cancer therapeutics.
Keywords:
anthocyanin oligomersapoptosisautophagybreast cancer cells

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