title: Effect of evodiagenine mediates photocytotoxicity on human breast cancer cells MDA-MB-231 through inhibition of PI3K/AKT/mTOR and activation of p38 pathways.
abstract: 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.
authors.affiliation: Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: Changliang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Jiangsu Center for Research & Development of Medicinal Plants, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, PR China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Jiangsu Center for Research & Development of Medicinal Plants, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address: boyun1987@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010778:Photochemotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C000597674:evodiagenine; C546842:MTOR protein, human
keywords: Apoptosis; Evodiagenine; PI3K/AKT/mTOR; Photocytotoxicity; p38