Ecliptasaponin A induces apoptosis through the activation of ASK1/JNK pathway and autophagy in human lung cancer cells

Background: Non-small cell lung Cancer (NSCLC) is one of the causes of carcinomas mortality worldwide. Ecliptasaponin A (ES), a natural product extracted from the plant known as Eclipta prostrata, has been reported as an anti-cancer drug against various Cancer cell lines. However, the exact mechanisms of ES have not yet been fully characterized.

Methods: Numerous studies have been done to support that ES has a powerful inhibiting effect on the growth of cancers via the activation of Apoptosis and Autophagy. To explore the underlying mechanisms of anti-cancer and investigate the relationships of the Apoptosis and Autophagy, we used Apoptosis signal-regulating kinase 1 (ASK1) inhibitor (GS-4997), c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and Autophagy inhibitor [chloroquine (CQ) and 3-methyladenine (3-MA)].

Results: ES could potently suppress cell viability and induces apoptotic cell death of human lung Cancer cells H460 and H1975. ES activated Apoptosis via ASK1/JNK pathway, GS-4997 and SP600125 can attenuated these effects. Furthermore, ES could triggered Autophagy in lung Cancer cell lines, and the Autophagy inhibitor 3-MA and CQ reversed ES-induced Apoptosis in H460 and H1975 cells. Furthermore, SP600125 can inhibit Autophagy.

Conclusions: This study showed that ES induces Apoptosis in human lung Cancer cells by triggering enhanced Autophagy and ASK1/JNK pathway, which may thus be a promising agent against lung Cancer.

Ecliptasaponin A (ES); Lung cancer; apoptosis; apoptosis signal-regulating kinase 1 (ASK1); autophagy; c-Jun N-terminal kinase (JNK).