Effect of evodiagenine mediates photocytotoxicity on human breast cancer cells MDA-MB-231 through inhibition of PI3K/AKT/mTOR and activation of p38 pathways

Photodynamic therapy (PDT), which is a form of phototherapy, uses nontoxic light-sensitive compounds which upon exposure to selective wavelength of light become toxic to the target cells. These compounds are used clinically to treat a wide range of malignant cancers, and are recognized as a treatment strategy which is both minimally invasive and less toxic, compared with other treatments available. Photodynamic therapy (PDT) might be a useful method in the management of malignant cancers. In this study, the photo-cytotoxicity of evodiagenine (EVO) mediated PDT on highly invasive and metastatic human breast cancer cells (MDA-MB-231) is examined. After incubating cancer cells with EVO, the cells are irradiated under ultraviolet-light for 120 min. EVO-PDT strongly inhibits the survival of breast cancer cells, increases the ROS production and enhanced LDH release. Western blot analysis was applied to quantify extent of phosphorylation of apoptosis-related proteins (PI3K/AKT/mTOR/p38). Our results indicate that the photocytotoxic effect of EVO may be through the inhibition of PI3K/AKT/mTOR phosphorylation and increasing p38 phosphorylation. It can be concluded that EVO may be a potential anticancer photo-sensitive agent for cancer treatment. (C) 2014 Elsevier B.V. All rights reserved.