Myricetin induces apoptosis through the MAPK pathway and regulates JNK­mediated autophagy in SK­BR­3 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 SK­BR­3 human breast cancer cells have not been elucidated. In the present study, the anticancer effects of myricetin were confirmed in human breast cancer SK­BR­3 cells. As the concentration of myricetin increased, the cell viability decreased. DAPI (4',6­diamidino­2­phenylindole) and Annexin V/PI staining also revealed a significant increase in apoptotic bodies and apoptosis. Western blot analysis was performed to confirm the myricetin­induced expression of apoptosis­related proteins. The levels of cleaved PARP and Bax proteins were increased, and that of Bcl­2 was decreased. The levels of proteins in the mitogen­activated protein kinase (MAPK) pathway were examined to confirm the mechanism of myricetin­induced apoptosis, and it was found that the expression levels of phosphorylated c­Jun N­terminal kinase (p­JNK) and phosphorylated mitogen­activated protein kinases (p­p38) were increased, whereas that of phosphorylated extracellular­regulated kinase (p­ERK) was decreased. It was also demonstrated that myricetin induced autophagy by promoting autophagy­related proteins such as microtubule­associated protein 1A/1B­light chain 3 (LC 3) and beclin 1. In addition, 3­methyladenine (3­MA) was used to evaluate the association between cell viability and autophagy in cells treated with myricetin. The results showed that simultaneous treatment with 3­MA 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 p­JNK, Bcl­2, and LC 3­II/I. These results suggest that myricetin induces apoptosis via the MAPK pathway and regulates JNK­mediated autophagy in SK­BR­3 cells. In conclusion, myricetin shows potential as a natural anticancer agent in SK­BR­3 cells.