Hyperthermia enhances tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human cancer cells.
OBJECTIVE
This study investigated whether hyperthermia can enhance TRAIL-induced apoptotic death.


METHODS
Human prostate adenocarcinoma DU-145, human pancreatic carcinoma MIA PaCa-2 and BxPC-3, human colon fibroblast CCD-33Co and rat prostate endothelial YPEN-1 cells were treated with various concentrations of TRAIL (0-200 ngml(-1)) with hyperthermia (40-42 degrees C).


RESULTS
It was observed in human cancer cells, but not in normal cells, that TRAIL induced apoptotic death and also that hyperthermia (40-42 degrees C) promoted TRAIL-induced apoptotic death. Enhancement of TRAIL-mediated apoptosis by hyperthermia was detected by an increase in PARP cleavage, the hallmark feature of apoptosis, as well as by activation of caspases. There were no significant changes in the intra-cellular levels of death receptors (DRs), decoy receptors (DcRs) and anti-apoptotic proteins. Interestingly, data from in vitro enzyme kinetics assay demonstrated that hyperthermia promoted caspase enzyme activity.


CONCLUSIONS
These data suggest that cancer cells are more susceptible to TRAIL in the condition of hyperthermia (40-42 degrees C). The promotion of caspase enzyme activity by hyperthermia may be responsible for enhancement of TRAIL-induced apoptotic death.
Yoo
Jinsang
J
Department of Surgery and Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Kim
Hyeong-Reh Choi
HR
Lee
Yong J
YJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001691:Biological Therapy; D020170:Caspase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D006979:Hyperthermia, Induced; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D011065:Poly(ADP-ribose) Polymerases; D020170:Caspase 1