Myricetin induces apoptosis through the MAPK pathway and regulates JNK‑mediated autophagy in SK‑BR‑3 cells.

Abstract

Myricetin, a flavonoid found in fruits and vegetables, is known to have antioxidant and anticancer effects. However, the anticancer effects of myricetin on SK-BR-3 human breast cancer cells have not been elucidated. In the present study, the anticancer effects of myricetin were confirmed in human breast cancer SK-BR-3 cells. As the concentration of myricetin increased, the cell viability decreased. DAPI (4′,6-diamidino-2-phenylindole) and Annexin V/PI staining also revealed a significant increase in apoptotic bodies and apoptosis. Western blot analysis was performed to confirm the myricetin-induced expression of apoptosis-related proteins. The levels of cleaved PARP and Bax proteins were increased, and that of Bcl-2 was decreased. The levels of proteins in the mitogen-activated protein kinase (MAPK) pathway were examined to confirm the mechanism of myricetin-induced apoptosis, and it was found that the expression levels of phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated mitogen-activated protein kinases (p-p38) were increased, whereas that of phosphorylated extracellular-regulated kinase (p-ERK) was decreased. It was also demonstrated that myricetin induced autophagy by promoting autophagy-related proteins such as microtubule-associated protein 1A/1B-light chain 3 (LC 3) and beclin 1. In addition, 3-methyladenine (3-MA) was used to evaluate the association between cell viability and autophagy in cells treated with myricetin. The results showed that simultaneous treatment with 3-MA and myricetin promoted the apoptosis of breast cancer cells. Furthermore, treatment with a JNK inhibitor reduced cell viability, promoted Bax expression, and reduced the expression of p-JNK, Bcl-2, and LC 3-II/I. These results suggest that myricetin induces apoptosis via the MAPK pathway and regulates JNK-mediated autophagy in SK-BR-3 cells. In conclusion, myricetin shows potential as a natural anticancer agent in SK-BR-3 cells.