Prodelphinidin from Purple Sweet Potato Induces Apoptosis in Human Triple-Negative Breast Cancer Cells via Reactive Oxygen Species and Endoplasmic Reticulum Stress Through the Mitochondrial Apoptosis Pathways

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Abstract

Triple negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, lacks an effective targeted therapy. Conventional medication has limited efficacy in treating TNBC, which highlights the potential of developing therapeutic agents from natural bioactive compounds. This study aimed to investigate the cytotoxicity of prodelphinidin (PD), an anthocyanin found in purple sweet potato, in human MDA-MB-231 and MDA-MB-436 cells. The results showed that PD selectively inhibited human breast cancer, particularly TNBC. Furthermore, PD demonstrated significant dose- and time-dependent inhibition of MDA-MB-231 and MDA-MB-436 cell activity. Flow cytometry and western blot analysis revealed that PD induced cell apoptosis by down-regulating Bcl-2, activating caspase-3/9, and cleaving PARP. Additionally, PD treatment upregulated the expression of p-elF2α, GRP78, and CHOP, indicating the involvement of endoplasmic reticulum stress (ERS). PD treatment also increased the production of reactive oxygen species (ROS) and decreased superoxide dismutase(SOD)activity in TNBC cells. The cytotoxicity of PD reduced significantly by pre-treatment with caspase inhibitors (Ac-DEVD-CHO and Z-LEHD-FMK). In conclusion, PD effectively inhibited the proliferation and induced apoptosis in TNBC cells through the activation of ROS and endoplasmic reticulum stress.

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