Hany A. Omar
University of Sharjah
United Arab Emirates
Title: Energy Restriction Synergizes Doxorubicin Activity via Targeting Breast Cancer Stem Cells
Biography
Biography: Hany A. Omar
Abstract
Unlike normal cells, cancer cells often shift their metabolism from oxidative phosphorylation to aerobic glycolysis as an adaptive response to intermittent hypoxia and the robust demand for energy production. However, the high need of glucose and the lack of flexibility in modifying energy resources make cancer cells extremely vulnerable to glucose starvation and energy restriction. Breast cancer stem cells (BCSCs) are known to mediate metastasis, resistance to radiation and chemotherapy, and contribute to relapse. The aim of the current work was to study to effect of energy-restriction mimetic agents (ERMAs) such as resveratrol and 2-deoxyglucose on the anticancer activity of doxorubicin in breast cancer cells. Methods: The antitumor effects of ERMAs and/or doxorubicin and the therapeutic combination were assessed by MTT assay, caspase activation, PARP cleavage, colony formation assay, immunofluorescence, and Western blot analysis. Percentage of ALDH1+/CD44+/CD24-/low in MDA-MB-231 cells was assessed by flow cytometry. Treatment with doxorubicin, while inhibited the cell viability, increased breast cancer ALDH1+/CD44+/CD24-/low cells. This stem cell-enriched population was declined and the anticancer effect of doxorubicin was significantly synergized by its combination with resveratrol or 2-deoxyglucose, suggesting that ERMAs preferentially inhibit stem/progenitors in breast cancer cells. Together, our results suggest that the targeting BCSCs population by ERMAs could be a rational strategy to minimize the resistance to doxorubicin.