Anti-invasion Effects of Cannabinoids Agonist and Antagonist on Human Breast Cancer Stem Cells

Iran J Pharm Res. Fall 2017;16(4):1479-1486.

Abstract

Studies show that cancer cell invasion or metastasis is the primary cause of death in malignancies including breast cancer. The existence of cancer stem cells (CSCs) in breast cancer may account for tumor initiation, progression, and metastasis. Recent studies have reported different effects of cannabinoids on cancer cells via CB1 and CB2 cannabinoid receptors. In the present study, the effects of ACEA (a selective CB1 receptor agonist) and AM251 (a selective CB1 antagonist) on CSCs and their parental cells were investigated. Breast CSCs derived from MDA-MB-231 cell line were sorted and characterized with CD44+/CD24-/low/ESA+ phenotype. It was observed that ACEA decreased CD44+/CD24-/low/ESA+ cancer stem cell invasiveness. Conversely, AM251 increased the invasion by more than 20% (at the highest concentrations) in both MDA-MB-231 and CSCs. Our results did not show any correlation between reduced invasion and cytotoxic effects of the drug. Since one of the main cancer recurrence factors is anti-cancer drugs fail to inhibit CSC population, this observation would be useful for cancer treatment.

Keywords: ACEA; AM251; Breast cancer stem cell; Cannabinoids; Invasion; MDA-MB-231.