title: The role of p38 in irinotecan-induced DNA damage and apoptosis of colon cancer cells.
abstract: The role of p38 in irinotecan (CPT-11)-induced damage and cell death in colon cancer cell line SW620 was investigated. We demonstrate that CPT-11 treatment activates p38 in exposed cells, however with concentration dependent dynamics and differing consequences. Higher CPT-11 concentrations induce a massive early but relatively short-lasting p38 activity leading to apoptosis mediated by mitochondria and caspases. Pharmacological or siRNA inhibition of p38 then significantly prevents CPT-11-dependent cell death. Conversely, lower CPT-11 concentrations activate p38 in a delayed, however sustained manner, with apoptosis occurring only in a fraction of cells and in the absence of significant autophagy. Blocking p38 in thus treated cells increases their sensitivity toward CPT-11 and increases cell death. In summary, our results confirm the involvement of p38 in colon cancer cells response to CPT-11 while indicating a varying role of p38 in the final biological response.
authors: Department of Medical Biology and Genetics, Charles University in Prague, Hradec Králové, Czech Republic. rudolf@lfhk.cuni.cz
authors: E
authors: E
authors: Rudolf
authors: V
authors: V
authors: Kralova
authors: K
authors: K
authors: Rudolf
authors: S
authors: S
authors: John
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D000077146:Irinotecan; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059008:Time-Lapse Imaging; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D000077146:Irinotecan; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D002166:Camptothecin