title: Role of p38MAPK in apoptosis and autophagy responses to photodynamic therapy with Chlorin e6.
abstract: BACKGROUND
  Photodynamic therapy (PDT) has been undergoing clinical evaluation for the treatment of colorectal cancer. But the molecular mechanism of photodynamic injury in human colorectal cancer cells still remains unclear.
  
  
  METHODS
  Chlorin e6 (Ce6) was used to photosensitize SW620 cells. The inhibitory effect of PDT was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide tetrazolium) assay and colony forming assay. Apoptosis was determined by nuclear DAPI (4'-6-diamidino-2-phenylindole) staining and Annexin V-PE/7-AAD assay. Monodansylcadaverine (MDC) staining was used to evaluate the abundance of autophagic vacuoles in PDT treated cells. The apoptosis and autophagy associated proteins were analyzed by western blotting. Moreover, we applied siRNA p38MAPK and p38MAPK inhibitor SB203580 to dissect its effect on cellular response to PDT in SW620 cells.
  
  
  RESULTS
  Ce6 mediated PDT (Ce6-PDT) induced apparent autophagy and apoptosis with dependent on ROS (reactive oxygen species) generation. When p38MAPK was inhibited by siRNA or inhibitor SB203580, a marked enhancement of apoptosis and autophagy in SW620 cells was detected after PDT. Moreover, autophagy inhibitor 3-methyladenine/Bafilomycin A1 greatly aggravated PDT induced photodamage in SW620 cells.
  
  
  CONCLUSIONS
  Ce6-PDT induced ROS production to activate p38MAPK probably to prevent SW620 cells from photodamage. Inhibition of p38MAPK activation accelerated cell apoptosis, meanwhile enhanced autophagy may act as a cytoprotective process in SW620 cells.
authors.affiliation: Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China; Department of Urology, Xijing Hospital, Fourth Military, Medical University, Xi'an, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China. Electronic address: wangxiaobing@snnu.edu.cn.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China. Electronic address: lshaof@snnu.edu.cn.
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002735:Chlorophyllides; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D048308:Mitogen-Activated Protein Kinase 14
keywords: Apoptosis; Autophagy; Ce6; PDT; p38MAPK