Stachydrine represses the proliferation and enhances cell cycle arrest and apoptosis of breast cancer cells via PLA2G2A/DCN axis

Considering the therapeutic efficacy of Stachydrine on breast cancer (BC), this study aims to decipher the relevant mechanism. The effects of Stachydrine on BC cell viability, proliferation and apoptosis were firstly investigated. Then, Bioinformatics was applied to sort out the candidate interacting with Stachydrine as well as its expression and downstream target in BC. Relative expressions of genes of interest as well as proliferation- and apoptosis-related factors in BC cells were quantified through quantitative reverse-transcription PCR and western blot as appropriate. As a result, Stachydrine inhibited the proliferation, down-regulated the expressions of proliferating cell nuclear antigen and CyclinD1, enhanced cell cycle arrest and apoptosis, and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9 in BC cells. Phospholipase A2 Group IIA (PLA2G2A) was predicted as the candidate interacting with Stachydrine and to be lowly expressed in BC. PLA2G2A silencing reversed while PLA2G2A overexpression reinforced the effects of Stachydrine. Decorin (DCN) was the downstream target of PLA2G2A and also lowly expressed in BC. PLA2G2A silencing counteracted yet overexpressed PLA2G2A strengthened the promoting effects of Stachydrine on DCN level. Collectively, Stachydrine inhibits the growth of BC cells to promote cell cycle arrest and apoptosis via PLA2G2A/DCN axis. Herbal medicine has become a safe, non-toxic and easily available source of cancer-treating compounds. Chinese motherwort (YiMuCao, Leonurus japonicus) is a traditional Chinese herb showing beneficial effects for obstetrical and gynecological diseases. Among the active compounds, Stachydrine has been widely investigated, which makes us wonder whether Stachydrine can also exert its tumor-suppressive effects on BC. Thankfully, existing studies have proved the anti-BC efficacy of Stachydrine on BC. Here, we additionally proved that Stachydrine inhibits the growth of BC cells to promote cell cycle arrest and apoptosis via PLA2G2A/DCN axis.image