Holothuria scabra Extract Induces Cell Apoptosis and Suppresses Warburg Effect by Down-Regulating Akt/mTOR/HIF-1 Axis in MDA-MB-231 Breast Cancer Cells.

INTRODUCTION Cancer cells utilize the modified glucose metabolism known as Warburg effect, with lactate production as the end product. In the search for alternative therapy, the body wall of sea cucumbers contains various substances with pharmacological activities. Herein, we investigate the effect of Holothuria scabra extract on the viability and Warburg effect of aggressive breast cancer cells. METHODS Body wall of H. scabra was extracted using 95% ethanol. Triple-negative breast cancer cells, MDA-MB-231, were treated with the extract at various concentrations under normoglycemic and hyperglycemic conditions. Cytotoxicity test was performed using MTT assay. Apoptotic proteins were quantified using Western blot. Apoptotic cells were stained with Hoechst 33342. Lactate production was determined using L-lactate assay kit. RESULTS By MTT assay, H. scabra extract suppressed the viability of breast cancer cells in a dose-dependent and time-dependent manner by enhancing apoptosis, indicated by a marked increase of proapoptotic Bax and pro-caspase three expressions, and decreased expression of anti-apoptotic Bcl-2. The extract could reduce hexokinase II expression, leading to reduced lactate production by blocking the Akt/mTOR/HIF-1 axis. DISCUSSION Overall findings indicated that H. scabra extract could be a possible therapeutic against breast cancer progression in patients with hyperglycemia, for instance, diabetes mellitus.