Sugiol suppresses the growth, migration, and invasion of human endometrial cancer cells via induction of apoptosis and autophagy.

Abstract

Recently, diterpenoids have been shown to exhibit several health benefits including cancer prevention. In the present study, we examined the anticancer effects of sugiol diterpene against the endometrial carcinoma and attempted to explore the underlying mechanisms. The results showed that sugiol significantly (P < 0.05) inhibited the proliferation of the endometrial carcinoma cell lines (HEC-1-A, HEC-1-B, and KLE) as compared to the normal THESCs cells. The IC50 of sugiol against all the three endometrial carcinoma cell lines ranged between 14 and 18µM as against an IC50 of 110μM against the normal THESCs cells. Sugiol caused several changes in the morphology of the HEC-1-B cells characteristic of apoptosis. The DAPI and annexin PI assays confirmed the induction of apoptosis in HEC-1-B cells. Sugiol also triggered increase in Bax and decrease in Bcl-2 expression. The acridine orange staining revealed that the formation of autolysosomes in HEC-1-B cells upon treatment with sugiol suggestive of autophagy. The autophagy was further confirmed by increase in the expression of LC3B-II, Beclin-1, Atg5, and Atg12 and decrease in the expression of P62. The transwell assay showed that relative to the untreated HEC-1-B cells, the migration and invasion of the sugiol-treated HEC-1-B cells was significantly (P < 0.05) inhibited. Collectively, the finding of the present study revealed that sugiol suppresses the growth of human endometrial cells via induction of apoptosis and autophagy. Consistently, sugiol may prove to be an important lead molecule in the development of chemotherapy for endometrial carcinoma.