Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells.
Source
College of Engineering, Peking University, Beijing 100871, China.
Abstract
This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells. The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis. Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations. Cannabisin B-induced changes in cell viability were completely inhibited by pre-treatment with 3-methyladenine (3-MA), indicating that the induction of autophagy by cannabisin B caused cell death. Additionally, cannabisin B induced S phase cell cycle arrest in a dose-dependent manner. Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down-stream targets of the mammalian target of rapamycin (mTOR). These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Copyright © 2012 Elsevier Ltd. All rights reserved.
- PMID:
- 23411211
- [PubMed – indexed for MEDLINE]
MeSH Terms, Substances
MeSH Terms
- Autophagy/drug effects*
- Cannabis/chemistry*
- Down-Regulation/drug effects
- Hep G2 Cells
- Humans
- Plant Extracts/pharmacology*
- Proto-Oncogene Proteins c-akt/genetics
- Proto-Oncogene Proteins c-akt/metabolism*
- S Phase Cell Cycle Checkpoints/drug effects*
- Seeds/chemistry*
- Signal Transduction/drug effects
- TOR Serine-Threonine Kinases/genetics
- TOR Serine-Threonine Kinases/metabolism*