Abstract
8-p-Hdroxybenzoyl tovarol (TAW) is a germacrane-type sesquiterpenoid that can be isolated from the roots of Ferula dissecta (Ledeb.) Ledeb. In this study, the growth inhibitory effects induced by TAW were screened on some types of tumor cells, and the mechanism was investigated on TAW-induced growth inhibition, including paraptosis and autophagy in human cervical cancer HeLa cells. TAW-induced paraptosis involved extensive cytoplasmic vacuolization in the absence of caspase activation. Additionally, TAW evoked cell paraptotic death mediated by endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Autophagy induced by TAW was found to antagonize paraptosis in HeLa cells. This effect was enhanced by rapamycin and suppressed by the autophagy inhibitor, 3-methyladenine (3MA). Loss of beclin 1 (an autophagic regulator) function led to promote ER stress. Taken together, these results suggest that TAW induces paraptosis like cell death and protective autophagy in HeLa cells, which would provide a new clue for exploiting TAW as a promising agent for the treatment of cervical cancer.
Highlights
Natural products have been the main source of traditional medicine since ancient time
The Ferula genus, belonging to the family of Apiaceae, has been reported to be rich in biologically active compounds such as terpenoid coumarins and sesquiterpene derivatives [1,2,3,4]. These compounds have been proven to be cytotoxic on several cancer cell lines and seem to be promising natural products for treatment of human cancers [5,6]. 8-p-Hdroxybenzoyl tovarol (TAW), a germacrane-type sesquiterpenoid, was isolated from the roots of Ferula dissecta (Ledeb.)
We demonstrated for the first time that TAW induces paraptosis characterized by cell death in conjunction with cytoplasmic vacuolation, no involvement of caspase activation and DNA fragmentation, dilated endoplasmic reticulum (ER) and mitochondria, and induction of ER stress and unfolded protein response (UPR) signaling markers
Summary
Natural products have been the main source of traditional medicine since ancient time. The Ferula genus, belonging to the family of Apiaceae, has been reported to be rich in biologically active compounds such as terpenoid coumarins and sesquiterpene derivatives [1,2,3,4] These compounds have been proven to be cytotoxic on several cancer cell lines and seem to be promising natural products for treatment of human cancers [5,6]. We demonstrated for the first time that TAW induces paraptosis characterized by cell death in conjunction with cytoplasmic vacuolation, no involvement of caspase activation and DNA fragmentation, dilated ER and mitochondria, and induction of ER stress and unfolded protein response (UPR) signaling markers. These results suggest that TAW induces paraptosis like cell death and protective autophagy in HeLa cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
