title: Targeted inhibition of p38MAPK-enhanced autophagy in SW620 cells resistant to photodynamic therapy-induced apoptosis.
abstract: Photodynamic therapy (PDT) is a promising and noninvasive treatment that can induce apoptosis, autophagy, or both depending on the cell phenotype. In this work, chlorin e6 (Ce6) was used to photosensitize human colorectal cancer SW620 cells. In cells, apparent autophagy and apoptosis with dependence on intracellular reactive oxygen species (ROS) generation were detected. p38MAPK activation followed by ROS generation might be a core component in Ce6 mediate PDT (Ce6-PDT)-induced autophagy and apoptosis signaling pathway. By using p38MAPK siRNA, the results showed a marked enhancement on cell apoptosis in Ce6-PDT with increased annexin (+) apoptotic cells, nuclear condensation, caspase-3, and PARP cleavage. Besides, impairment of p38MAPK also promoted the autophagic response to photodamage as indicated by conversion of LC3 and monodansyl cadaverine (MDC) labeling patterns. It appears that Ce6-PDT induced ROS production involving activation of p38MAPK, probably to prevent SW620 cells from photodamage. Moreover, autophagy inhibitor 3-methyladenine/bafilomycin A1 greatly aggravated Ce6-PDT-induced apoptosis in SW620 cells with knockdown of p38MAPK. Taken together, this study suggests that autophagy could represent a promising field in cancer treatment and p38MAPK may be a potential therapeutic target to enhance the efficacy on clinical evaluation for the treatment of colorectal cancer.
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: Qin
authors.initials: Q
authors.lastname: Xue
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D055785:Gene Knockdown Techniques; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C062985:phytochlorin; D048051:p38 Mitogen-Activated Protein Kinases