Related Experiment Videos
PI3K/Akt pathway activation attenuates the cytotoxic effect of methyl jasmonate toward sarcoma cells
1Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Abstract:
Methyl jasmonate (MJ) acts both in vitro and in vivo against various cancer cell lines. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway results in decreased susceptibility to cytotoxic agents in many types of cancer cells. We found a strong inverse correlation between the basal level of phospho-Akt (pAkt) and the sensitivity to MJ among sarcoma cell lines. Nevertheless, levels of pAkt increased in two sarcoma cell lines, MCA-105 and SaOS-2, after MJ treatment. Treatment of both cell lines with PI3K/Akt pathway inhibitors in combination with MJ resulted in a synergistic cytotoxic effect. Moreover, cells transfected with a constitutively active Akt were less susceptible to MJ-induced cytotoxicity in comparison with cells transfected with an inactive form of Akt. Taken together, these data suggest that the increase in pAkt after treatment with MJ played a protective role. Because it has been shown that the antiapoptotic effects of Akt are dependent on glycolysis, we examined the role of glucose metabolism in activation of Akt and the subsequent resistance of the cell lines to MJ. 2-Deoxy-d-glucose, a glycolysis inhibitor, decreased the levels of pAkt and was able to attenuate the MJ-induced elevation in pAkt. Accordingly, the presence of glucose attenuated MJ-induced cytotoxicity. Moreover, treatment with 2-deoxy-d-glucose in combination with MJ resulted in a synergistic cytotoxic effect. In conclusion, the PI3K/Akt pathway plays a critical role in the resistance of MCA-105 and SaOS-2 sarcoma cell lines toward MJ-induced cytotoxicity.
Related Concept Videos
The JAK-STAT Signaling Pathway
PI3K/mTOR/AKT Signaling Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
MAPK Signaling Cascades