Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Effect of punicalagin on the autophagic cell death in triple-negative breast cancer cells

  • Zeeshan Ahmad Bhutta (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Ryeo‑Eun Go (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Kyung‑Chul Choi (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
  • Received : 2024.01.25
  • Accepted : 2024.05.01
  • Published : 2024.10.15
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Abstract

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), resulting in poor clinical outcomes and high mortality. The present study was aimed to evaluate the efficacy of Punicalagin (PCG), a polyphenol obtained from the Punica granatum, against TNBC. We evaluated the therapeutic potential of PCG in TNBC (MDA-MB-231, BT-20) and ER+(MCF-7) breast cancer cells. A dose-dependent inhibition of MDA-MB-231 cell proliferation was observed with PCG (12.5-100 µM). However, only 50 and 100 µM doses of PCG inhibited the growth of BT-20 and MCF-7 cells. PCG significantly increased mitochondrial ROS in TNBC cells and induced autophagy across all cell lines, as evidenced by an increase in autophagic vacuoles and a decrease in the ratio of LC3-II/LC3-I. PCG suppressed PI3K/Akt and activated phosphorylated c-Jun N-terminal kinase (p-JNK) signaling. Based on these findings, it can be concluded that PCG is capable of significantly inhibiting the proliferation of TNBC cells through the suppression of the PI3K/Akt pathway as well as the initiation of the JNK pathway. PCG could thus be potentially useful as a therapeutic agent for the treatment of TNBC.

Keywords

Acknowledgement

This work was supported by the Basic Research Lab Program (2022R1A4A1025557) through the National Research Foundation (NRF) of Korea, funded by the Ministry of Science and ICT. In addition, this study was also supported by the "Regional Innovation Strategy (RIS)" through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE; 2021RIS-001) in 2024.

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