Back to Search
Start Over
Bufalin induces protective autophagy by Cbl-b regulating mTOR and ERK signaling pathways in gastric cancer cells.
- Source :
-
Cell biology international [Cell Biol Int] 2019 Jan; Vol. 43 (1), pp. 33-43. - Publication Year :
- 2019
-
Abstract
- Bufalin, a natural small-molecule compound derived from the traditional Chinese medicine Chan su, has shown promising anti-cancer effects against a broad variety of cancer cells through different mechanisms. It has been reported to induce autophagy in gastric cancer cells. However, the molecular mechanism involved is not fully elucidated. In the present study, we aimed to investigate the molecular mechanism by which bufalin induce autophagy in human gastric cancer cells. We found that bufalin induced apoptosis and autophagy in gastric cancer cells, and autophagy prevented human gastric cancer cells from undergoing apoptosis. Bufalin treatment changed the expression of autophagy-related proteins. Moreover, phosphorylated Akt, mTOR, and p70S6K were all significantly decreased, while phosphorylated ERK1/2 was increased by bufalin. Pretreatment of MGC803 cells with the ERK1/2-specific inhibitor PD98059 led to the down-regulation of LC3 II. Further study showed that Cbl-b positively regulated autophagy by suppressing mTOR and enhancing ERK1/2 activation. Therefore, our data provide evidence that bufalin induces autophagy in MGC803 cells via both Akt/mTOR/p70S6K and ERK signaling pathways, and Cbl-b-mediated suppression of mTOR and activation of ERK1/2 might play an important role.<br /> (© 2018 International Federation for Cell Biology.)
- Subjects :
- Apoptosis drug effects
Autophagy-Related Proteins metabolism
Cell Line, Tumor
Cell Survival drug effects
Humans
Proto-Oncogene Proteins c-akt metabolism
Ribosomal Protein S6 Kinases, 70-kDa metabolism
Stomach Neoplasms ultrastructure
Autophagy drug effects
Bufanolides pharmacology
MAP Kinase Signaling System drug effects
Proto-Oncogene Proteins c-cbl metabolism
Stomach Neoplasms pathology
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8355
- Volume :
- 43
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell biology international
- Publication Type :
- Academic Journal
- Accession number :
- 30468278
- Full Text :
- https://doi.org/10.1002/cbin.11076