Moxonidine an Antihypertensive Agent Sensitizes Cancer Cells to Apoptosis

There is an emerging link between diabetes and periodontal disease, and between diabetes and cancer. Sulfonylurea drugs used to treat type 2 diabetes cause release of insulin, and are associated with an increased risk of oral cancer. Metformin which is an insulin sensitizer, is not associated with an increased risk of oral cancer, but is reported to induce apoptosis in triple negative breast cancer cells. Moxonidine is an imidazoline agonist used clinically to treat hypertension, and has insulin sensitizing effects. Objectives: To investigate whether moxonidine treatment may sensitize breast cancer cells to the apoptotic effect of known anticancer agents. Methods: MDA-MB-468 triple negative breast cancer cells were treated for 24 hr with either vehicle (0.1% DMSO), camptothecin (1µM), moxonidine (1µM), or pretreatment with moxonidine(1µM) for 2hr followed by addition of camptothecin (1µM) in the presence of moxonidine(1µM). Other cells were treated with vehicle (0.1% DMSO), aminoflavone (1µM), moxonidine (1µM) or pretreatment with moxonidine(1µM) for 2hr followed by addition of aminoflavone (1µM) in the presence of moxonidine(1µM). Treated cells were detached by trypsinization and counted using a Coulter counter. Percentage growth inhibition was determined by comparison of cell number per well in treated versus control cells. Results: Our data showed that moxonidine in combination with the anticancer agents camptothecin or aminoflavone, significantly induced more apoptosis in breast cancer cells than when the anticancer agents were used alone. Moxonidine alone did not significantly reduce cell numbers. Conclusions: Moxonidine treatment sensitized breast cancer cells to the apoptotic effects of anticancer agents such as camptothecin and aminoflavone. These results suggest that expanded use of insulin sensitizing agents such as metformin or moxonidine to treat type 2 diabetes, may reduce the risk of oral cancer associated with agents that cause insulin release, and also benefit the treatment of other types of cancer.