Effects of trimetazidine on anticancer activity and toxicity of abraxane in MCF-7 breast cancer cells

Abstract

Trimetazidine, an anti-ischemic agent, can increase the use of glucose for ATP production in the cells by shifting energy metabolism from fatty acid oxidation to glucose oxidation. There is very limited research investigating the possible antitumoral potential of trimetazidine in breast cancer cells when used alone and/or together with different chemotherapeutic drugs. We investigated the effects of trimetazidine alone or in combination with abraxane on cell viability, apoptosis, and ATP levels in human breast cancer cells. The cells treated with trimetazidine (50, 100 and 250 mu M) separately or together with abraxane (1 mu M) for 24, 48 and 72 h. Greater cytotoxicity was observed in the combined treatment of trimetazidine + abraxane than that of abraxane used alone for 48 and 72 h. Trimetazidine alone or together with abraxane increased apoptosis rates for all treatment times but trimetazidine + abraxane induced apoptosis more than abraxane alone for 72 h. While trimetazidine increased the level of ATP at low concentration, the level of ATP decreased depending on the concentration increase. When 100 mu M or 250 mu M trimetazidine used with abraxane, significant decreases were found in ATP levels for longer treatments. These results indicated that co-treatment of abraxane with especially high trimetazidine concentrations and long treatment times can induce the death of breast cancer cells. A combination strategy based on trimetazidine and anticancer drugs may be more effective in the treatment of breast cancers.