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

Fitoterapia. 2014 Dec:99:292-9. doi: 10.1016/j.fitote.2014.10.010. Epub 2014 Oct 16.

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.

Keywords: Apoptosis; Evodiagenine; PI3K/AKT/mTOR; Photocytotoxicity; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • Molecular Structure
  • Oxidative Stress
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Photochemotherapy*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism
  • Ultraviolet Rays
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds, 4 or More Rings
  • Reactive Oxygen Species
  • evodiagenine
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases