Trichostatin A increases the thermosensitivity of human glioblastoma A172 cells.
Trichostatin A (TSA), histone deacetylase inhibitor, shows a promising therapeutic effect on cancer cells in combination with radiotherapy or chemotherapy. However, little has been reported on the combined treatment of TSA with hyperthermia. Here, we have assessed the effect of TSA/hyperthermia on human glioblastoma A172 cells and found that TSA increases the thermosensitivity of A172 cells, resulting in cellular apoptosis. The underlying mechanism of this effect consists of reduction in the level of phosphorylated STAT3 (Tyr705), a transcription factor required for survival of A172 cells, which leads to down-regulation of STAT3 target genes, cyclin D1 and Bcl-xL. Furthermore, the level of VEGF mRNA was also decreased by TSA/hyperthermia, suggesting the antiangiogenic effect of TSA/hyperthermia on human glioblastoma. Collectively, our results show the role of TSA as a chemical thermosensitizer, suggesting the possible therapeutic application of combined treatment of TSA/hyperthermia on STAT3-dependent tumors.
Baek
Sun-Yong
SY
Department of Anatomy, College of Medicine, Pusan National University, Busan 602-739, South Korea.
Kim
Su-Ryun
SR
Bae
Moon-Kyoung
MK
Hwang
Jee-Won
JW
Kim
Jeong-Sam
JS
Choi
Yung Hyun
YH
Wee
Hee-Jun
HJ
Kim
Bong-Seon
BS
Kim
Jae-Bong
JB
Yoon
Sik
S
Bae
Soo-Kyung
SK
D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000188:drug therapy; D005434:Flow Cytometry / Q000379:methods; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013696:Temperature; D013697:Thermosensing / Q000187:drug effects*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; C012589:trichostatin A