Enhancing the Therapeutic Efficacy of 2-Deoxyglucose in Breast Cancer Cells Using Cell-cycle Synchronization

Abstract

AIM: We assessed the effect of cell-cycle synchronization using the T-type calcium channel inhibitor mibefradil on the anticancer effects of 2-deoxy-D-glucose (2-DG) and glucose metabolism in breast cancer cells. MATERIALS AND METHODS: MDA-MB-231 cells were treated with mibefradil, followed by 2-DG with/without paclitaxel, then cells were assessed for viability. Glucose metabolism was evaluated by (3)H-2-DG uptake, lactate concentration, and membrane glucose transporter 1 expression after mibefradil treatment. RESULTS: Viability was significantly lower in cells receiving the combination therapy of mibefradil and 2-DG relative to 2-DG treatment alone: addition of paclitaxel to the combination therapy further reduced the viability of breast cancer cells. Withdrawal of mibefradil resulted in a significant increase in cellular (3)H-2-DG uptake uptake, a slight accumulation of lactate, and increased membrane glucose transporter 1 expression. CONCLUSION: Mibefradil-induced cell-cycle synchronization enhanced the anticancer activity of 2-DG in breast cancer cells due to an increase in cellular glucose metabolism.