Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

Abstract

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. [Mol Cancer Ther 2007;6(11):2921 -7]

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

“…CBD could down-regulate the Id-1 expression in aggressive human breast cancer cells, and the concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. 113 The precise mechanisms underlying CBD effects on apoptosis and tumor growth are not clear, and have recently been discussed in a review by Mechoulam. 12 CBD: a drug with multiple mechanisms of action The plethora of CBD effects described above can be explained by its multiple mechanisms of action.…”

COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells

“…In a panel of tumor cell lines, cannabidiol even exhibited the most potent antiproliferative action as compared with a variety of other cannabinoids (3). Moreover, cannabidiol has been proven to exert anti-invasive properties on cervical (8), lung (9,10), and breast cancer cells (11) in vitro, an antimetastatic action on lung (8,10) and breast cancer cells (3), as well as tumor-regressive effects on solid tumors in vivo (3,9,10). Apart from its direct antitumorigenic action, cannabidiol has recently also been shown to relieve intractable and opioid-insensitive cancer pain (12) and to reduce severe adverse reactions associated with chemotherapy such as neurotoxic and nephrotoxic effects (13,14).…”

Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1

“…5 In context with the antitumorigenic action of cannabinoids, modulation of cancer cell invasion has recently emerged as a topic of increasing interest [21][22][23]. Cancer cell invasion is a complex process of cell locomotion through degraded matrix components of microenvironmental spaces surrounding a tumor thereby contributing to tumor cell metastasis and angiogenesis.…”