Delphinidin induces cell cycle arrest and apoptosis in HER-2 positive breast cancer cell lines by regulating the NF-κB and MAPK signaling pathways

Oncol Lett. 2021 Dec;22(6):832. doi: 10.3892/ol.2021.13093. Epub 2021 Oct 14.

Abstract

Delphinidin is an anthocyanidin monomer, commonly found in vegetables and fruits, and has demonstrated antitumor effects in the HER-2-positive MDA-MB-453 breast cancer cell line, with low cytotoxicity on normal breast cells. However, the direct functional mechanisms underlying the effect of delphinidin on HER-2-positive breast cancer cells has not been fully characterized. In the present study, it was found that delphinidin could induce G2/M phase cell cycle arrest by inhibiting the protein expression level of cyclin B1 and Cdk1 in HER-2-positive breast cancer cell lines. In addition, delphinidin promoted the mitochondrial apoptosis pathway by inhibiting the ERK and NF-κB signaling pathway and activating the JNK signaling pathway. Therefore, delphinidin markedly suppressed the viability of the HER-2-positive breast cancer cell lines by modulating the cell cycle and inducing apoptosis. Overall, the findings from the present study demonstrated that delphinidin treatment could induce the mitochondrial apoptosis pathway in human HER-2-positive breast cancer cell lines, providing an experimental basis for the prevention and treatment of HER-2-positive breast cancer by flavonoids.

Keywords: HER-2-positive breast cancer; MAPK signaling pathway; NF-κB signaling pathway; apoptosis; cell cycle arrest; delphinidin.

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant nos. 81573154, 82073539 and 81773432).