Sesamin induces ER stress-mediated apoptosis and activates autophagy in cervical cancer cells

Aims: Sesamin, a major lignan of sesame oil, has demonstrated anticancer properties. However, its anticancer effects on cervical cancer have not been studied. Here, we investigated the effects of sesamin on cervical cancer (HeLa) cell line and explored the underlying mechanisms. Main methods: HeLa cells were cultured with sesamin. CCK-8 and scratch wound test were applied to detect the proliferation and migration ability, while flow cytometry and TUNEL staining were applied to detect apoptosis. The expression of Bax and Bcl-2 was assessed by Western blotting. Further observe the ultrastructure using transmission electron microscopy (TEM) and detect the expression of caspase-12, GRP78, GADD153, IRE1 alpha, p-IRE1 alpha, JNK, p-JNK, LC3I/II and beclin-1. In addition, HeLa cells were treated with 3-MA (an autophagy inhibitor) and/or sesamin. Then detect the expression of LC3I/II and cell viability. Key findings: CCK-8 and scratch wound test revealed that sesamin inhibits HeLa cells proliferation and migration, while flow cytometry and TUNEL staining indicated that sesamin induces apoptosis in these cells. In sesamin group, the expression of Bax, caspase-12, GRP78, GADD153, p-IRE1 alpha, p-JNK, LC3I/II and beclin-1 was up-regulated while Bcl-2 was down-regulated compared to control group. Further research revealed that sesamin also induces Hela cells autophagy and inhibition of autophagy increases cell viability of sesamin-treated HeLa cells. Significance: Sesamin inhibits proliferation/migration of HeLa cells and induces ER stress-mediated apoptosis through IRE1 alpha/JNK pathway, and that it activates autophagy and autophagic death in these cells, further validate the anticancer effect of sesamin.