Heat shock protects HCT116 and H460 cells from TRAIL-induced apoptosis.
Heat shock proteins have been shown to protect cells from a variety of stressful conditions, including hyperthermia, oxidative and DNA damage, serum withdrawal, and a variety of chemicals. HSP27, HSP70, and HSP90 have been shown to downregulate different aspects of apoptosome assembly. TRAIL is a member of the TNF family of ligands and is a promising anti-cancer agent. It has been shown to be nontoxic to most normal cell types, while it is a potent killer of many different cancer cells. TRAIL engages both the receptor-mediated (extrinsic) and the mitochondria-initiated (intrinsic) cascades. We tested whether heat shock affects TRAIL-induced apoptosis in different cancer cells. TRAIL treatment does not induce HSP27, HSP70, or HSP90 levels. Nonetheless, when treated with TRAIL for 3 h after release from heat shock, the human colon cancer cell line HCT116 is protected from apoptosis whereas the human colon cancer cell line SW480 is not. This pattern is consistent with the previously observed behavior of HCT116 as Type II cells that depend on mitochondrial signaling and SW480 as Type I, whose TRAIL-induced death is not sensitive to inhibition of caspase 9. Moreover, the failure of heat shock to protect SW480 cells is not due to a lack of HSP70 or HSP90 upregulation. HSP70 and HSP90 are induced 3 h after release from heat shock, whereas HSP27 is induced much later. Thus, the observed protective effect against TRAIL is probably due to the anti-apoptotic effects of HSP70 and HSP90. These results further illustrate interactions between TRAIL receptor signaling and the intrinsic cell death pathway and have practical implications for the potential use of TRAIL and hyperthermia in cancer therapy.
Ozören
Nesrin
N
Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
El-Deiry
Wafik
W
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D004792:Enzyme Precursors / Q000187:drug effects / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006979:Hyperthermia, Induced; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004792:Enzyme Precursors; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases