Potential of Orlistat to induce apoptotic and antiangiogenic effects as well as inhibition of fatty acid synthesis in breast cancer cells

Abstract

Breast cancer as most often women's cancer is the second cause of mortality worldwide. Research interest increased in testing non-standard drugs to suppress breast cancer progression and become significant supplements in anticancer therapy. The anti-obesity drug Orlistat showed significant ability for modulation of cancer cell metabolism via antiproliferative, proapoptotic, antiangiogenic, antimetastatic, and hypolipidemic effects. The anticancer potential of Orlistat was evaluated by cytotoxicity (MTT assay), type of cell death (AO/EB double staining), determination of redox status parameters (superoxide, hydrogen peroxide, lipid peroxidation, reduced glutathione), and total lipid levels with colorimetric methods, as well on angiogenesis-related (VEGF, MMP-9, CXCR4/CXCL12) and fatty acid synthesis-related (ACLY, ACC, FASN) parameters on gene and protein levels (immunocytochemistry and qPCR). Based on obtained results Orlistat induces significant cytotoxic, proapoptotic, and anti-angiogenic effects in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells, without significant cytotoxic effects on normal MRC-5 cells. It decreased total lipid levels and changed redox status parameters and cancer cell metabolism via suppression of genes and proteins involved and fatty acid synthesis. Based on showed, Orlistat may be an important supplement in antiangiogenic therapy against breast cancer with no side effects on normal cells, making it a good candidate for future clinical trials.