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(-)-Guaiol regulates autophagic cell death depending on mTOR signaling in NSCLC.
- Source :
-
Cancer biology & therapy [Cancer Biol Ther] 2018 Aug 03; Vol. 19 (8), pp. 706-714. Date of Electronic Publication: 2018 Apr 19. - Publication Year :
- 2018
-
Abstract
- (-)-Guaiol, a sesquiterpene alcohol with the guaiane skeleton, has been found in many Chinese medicinal plants and been reported to comprise various guaiane natural products that are well known for their antibacterial activities. Previously, we have shown its antitumor activity by inducing autophagy in NSCLC cells. However, its potential mechanism in inducing autophagy is still under our investigation. Here, data from our western blotting assays showed that, in NSCLC cells, (-)-Guaiol significantly blocked the mTORC2-AKT signaling by suppressing mTOR phosphorylation at serine 2481 (S2481) to induce autophagy, illustrated by the increasing ratio of LC3II/I. Besides, it impaired the mTORC1 signaling by inhibiting the activity of its downstream factors, such as 4E-BP1 and p70 S6K, all of which could obviously rescued by the mTOR activator MHY1485. Afterwards, results from biofunctional assays, including cell survival analysis, colony formation assays and flow cytometry assays, suggested that (-)-Guaiol triggered autophagic cell death by targeting both mTORC1 and mTORC2 signaling pathways. In summary, our studies showed that (-)-Guaiol inhibited the proliferation of NSCLC cells by specifically targeting mTOR signaling pathways, including both mTORC1 and mTORC2 signaling, providing a better therapeutic option for substituting rapamycin in treating NSCLC patients.
- Subjects :
- Cell Line, Tumor
Cell Survival drug effects
Humans
Mechanistic Target of Rapamycin Complex 2 metabolism
Models, Biological
Sesquiterpenes, Guaiane
Autophagy drug effects
Carcinoma, Non-Small-Cell Lung metabolism
Lung Neoplasms metabolism
Sesquiterpenes pharmacology
Signal Transduction drug effects
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1555-8576
- Volume :
- 19
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer biology & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 29611762
- Full Text :
- https://doi.org/10.1080/15384047.2018.1451277