title: Fever-range hyperthermia vs. hypothermia effect on cancer cell viability, proliferation and HSP90 expression.
abstract: OBJECTIVE
  The current study examines the effect of fever-range hyperthermia and mild hypothermia on human cancer cells focusing on cell viability, proliferation and HSP90 expression.
  
  
  METHODS
  A549 and H1299 lung carcinoma, MCF7 breast adenocarcinoma, U87MG and T98G glioblastoma, DU145 and PC3 prostate carcinoma and MRC5 normal fetal lung fibroblasts cell lines were studied. After 3-day exposure to 34°C, 37°C and 40°C, cell viability was determined. Cell proliferation (ki67 index), apoptosis (Caspase 9) and HSP90 expression was studied by confocal microscopy.
  
  
  RESULTS
  Viability/proliferation experiments demonstrated that MRC5 fibroblasts were extremely sensitive to hyperthermia, while they were the most resistant to hypothermia. T98G and A549 were thermo-tolerant, the remaining being thermo-sensitive to a varying degree. Nonetheless, as a universal effect, hypothermia reduced viability/proliferation in all cell lines. Hyperthermia sharply induced Caspase 9 in the U87MG most thermo-sensitive cell line. In T98G and A549 thermo-tolerant cell lines, the levels of Caspase 9 declined. Moreover, hyperthermia strongly induced the HSP90 levels in T98G, whilst a sharp decrease was recorded in the thermo-sensitive PC3 and U87MG cell lines. Hyperthermia sensitized thermo-sensitive cancer cell lines to cisplatin and temozolomide, whilst its sensitizing effect was diminished in thermo-tolerant cell lines.
  
  
  CONCLUSIONS
  The existence of thermo-tolerant and thermo-sensitive cancer cell lines was confirmed, which further encourages research to classify human tumor thermic predilection for patient stratification in clinical trials. Of interest, mild hypothermia had a universal suppressing effect on cancer cell proliferation, further supporting the radio-sensitization hypothesis through reduction of oxygen and metabolic demands.
authors: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors: Dimitra
authors: D
authors: Kalamida
authors: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors: Ilias V
authors: IV
authors: Karagounis
authors: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors: Achilleas
authors: A
authors: Mitrakas
authors: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors: Sofia
authors: S
authors: Kalamida
authors: Department of Pathology, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors: Alexandra
authors: A
authors: Giatromanolaki
authors: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors: Michael I
authors: MI
authors: Koukourakis
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D003080:Cold Temperature; D058639:Cold-Shock Response; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D006358:Hot Temperature; D006801:Humans; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018841:HSP90 Heat-Shock Proteins; D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide
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