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: Qin Xue, Pan Wang, Xiaobing Wang, Kun Zhang, Quanhong Liu
• Journal: Lasers in medical science (Lasers Med Sci) Vol. 30 Issue 7 Pg. 1967-75 (Sep 2015) ISSN: 1435-604X [Electronic] England
• PMID: 26254783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chlorophyllides
• Photosensitizing Agents
• Porphyrins
• RNA, Small Interfering
• Reactive Oxygen Species
• phytochlorin
• p38 Mitogen-Activated Protein Kinases

Topics

• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chlorophyllides
• Colorectal Neoplasms (drug therapy)
• Drug Screening Assays, Antitumor
• Gene Knockdown Techniques
• Humans
• Photochemotherapy
• Photosensitizing Agents (pharmacology)
• Porphyrins (pharmacology)
• RNA, Small Interfering (genetics)
• Reactive Oxygen Species (metabolism)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)