Specialized Cell Structure and Function: Protein Synthesis
The ribosome is the site of protein synthesis ..
We have recently shown in culture that cannabidiol was an effective inhibitor of Id-1 expression and corresponding breast cancer cell aggressiveness, that is, invasion and proliferation (25, 26). To determine whether cannabidiol could inhibit Id-1 expression in aggressive brain cancers, U251 cells were treated with cannabidiol for 3 days and analyzed for Id-1 protein using Western blot analysis. In U251 cells, cannabidiol produced a concentration-dependent downregulation of Id-1 (Fig. 6A). In addition, the downregulation of Id-1 expression correlated with a concentration-dependent inhibition of U251 cell invasion (Fig. 6B). Similar activity was observed in primary glioblastoma cells that express Id-1 (Fig. 6C and D). Moreover, cannabidiol modulated the phosphorylation of several phospho-kinases in U251 cells, including AKT
In the next phase of protein synthesis, ..
Mol Cancer Ther. 2007 Nov;6(11):2921-7.
Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells.
McAllister SD1, Christian RT, Horowitz MP, Garcia A, Desprez PY.
Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.