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Inhibition of Nrf2 enhances the anticancer effect of 6-O-angeloylenolin in lung adenocarcinoma.
- Source :
-
Biochemical Pharmacology . Apr2017, Vol. 129, p43-53. 11p. - Publication Year :
- 2017
-
Abstract
- 6- O -Angeloylenolin (6-OA), a sesquiterpene lactone isolated from Centipeda minima (L.) A. Br. (Compositae), has been used to treat respiratory diseases for centuries. However, whether and how 6-OA exerts anticancer effects against lung cancer remains to be elucidated. In this study, we showed that 6-OA markedly suppressed the cell viability and colony formation of lung cancer cells H1299 and A549, with no significant toxic effect on non-cancer cells HBE. Annexin V/7-AAD assay revealed that 6-OA induced cell apoptosis in dose- and time-dependent manners, which was further confirmed by the increased expression of cleaved caspase-3. To uncover the molecular mechanism how 6-OA exerts its anticancer effects, SILAC quantitative proteomics was performed to identify 6-OA-regulated proteins in lung cancer cells. Ingenuity Pathway Analysis revealed that these 6-OA-regulated proteins were mainly involved in Nrf2-mediated oxidative stress response, which was confirmed by the nuclear translocation of Nrf2 upon 6-OA treatment. Moreover, we found that 6-OA stimulated the accumulation of reactive oxygen species (ROS), whereas inhibition of ROS generation with N-acetyl l -cysteine could block the 6-OA-induced anticancer effects. Furthermore, blockade of cellular anti-oxidative system by Nrf2 knockdown significantly augmented the 6-OA-induced apoptosis. Taken together, we demonstrated that 6-OA exerts its anticancer effects by generating ROS, and inhibition of Nrf2 anti-oxidative system potentiated these effects. These results suggest that 6-OA may be used to treat lung cancer, with better outcome by combining with Nrf2 inhibitor to block Nrf2 pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00062952
- Volume :
- 129
- Database :
- Academic Search Index
- Journal :
- Biochemical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 121493134
- Full Text :
- https://doi.org/10.1016/j.bcp.2017.01.006