Effect of Punicalagin on the Autophagic Cell Death in Triple-Negative Breast Cancer Cells

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.