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

Studies show that cancer cell invasion or metastasis is the primary cause of death inmalignancies including breast cancer. The existence of cancer stem cells (CSCs) in breast cancermay account for tumor initiation, progression, and metastasis. Recent studies have reporteddifferent effects of cannabinoids on cancer cells via CB1 and CB2 cannabinoid receptors. In thepresent study, the effects of ACEA (a selective CB1 receptor agonist) and AM251 (a selectiveCB1 antagonist) on CSCs and their parental cells were investigated. Breast CSCs derived fromMDA-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 reducedinvasion and cytotoxic effects of the drug. Since one of the main cancer recurrence factors isanti-cancer drugs fail to inhibit CSC population, this observation would be useful for cancertreatment.