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Title: Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines

Abstract

Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, microplate based, label-free detection approach. This study investigates how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32 °C, 37 °C and 42 °C using assay medium conditions and equipment settings adjusted to produce equal oxygen and pH levels ubiquitously at the beginning of all experiments. The results suggest that temperature significantly changes multiple components of glycolytic and mitochondrial function of all cell lines tested. Under hypothermia conditions (32 °C), the extracellular acidification rates (ECAR) of CRC cells were significantly lower compared to the same basal ECAR levels measured at 37 °C. Mitochondrial stress test for SW480 cells at 37 °C vs 42 °C demonstrated increased proton leak while all other OCR components remained unchanged (similar results were detected also for the patient-derived xenograftmore » cells Pt.93). Interestingly, the FCCP dose response at 37 °C vs 42 °C show significant shifts in profiles, suggesting that single dose FCCP experiments might not be sufficient to characterize the mitochondrial metabolic potential when comparing groups, conditions or treatments. These findings provide valuable insights for the metabolic and bioenergetic changes of CRC cells under hypo- and hyperthermia conditions that could potentially lead to development of better targeted and personalized strategies for patients undergoing combined thermotherapy with chemotherapy.« less

Authors:
 [1];  [2]; ;  [1];  [1];  [3];  [1];  [3]
  1. Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States)
  2. Department of Surgery, University of Kentucky, Lexington, KY 40506 (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
22649856
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 354; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACIDIFICATION; ADENOSINE; ATP; AUC; BIOLOGICAL STRESS; CARBONYLS; CHEMOTHERAPY; CLINICAL TRIALS; COMPARATIVE EVALUATIONS; CYANIDES; DOXORUBICIN; FUNCTIONS; GLYCOLYSIS; HYPERTHERMIA; HYPOTHERMIA; MITOCHONDRIA; NEOPLASMS; OXIDATION; OXYGEN; PATIENTS; PHOSPHORYLATION

Citation Formats

Mitov, Mihail I., E-mail: m.mitov@uky.edu, Harris, Jennifer W., Alstott, Michael C., Zaytseva, Yekaterina Y., Evers, B. Mark, Department of Surgery, University of Kentucky, Lexington, KY 40506, Butterfield, D. Allan, and Department of Chemistry, University of Kentucky, Lexington, KY 40506. Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.03.046.
Mitov, Mihail I., E-mail: m.mitov@uky.edu, Harris, Jennifer W., Alstott, Michael C., Zaytseva, Yekaterina Y., Evers, B. Mark, Department of Surgery, University of Kentucky, Lexington, KY 40506, Butterfield, D. Allan, & Department of Chemistry, University of Kentucky, Lexington, KY 40506. Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines. United States. doi:10.1016/J.YEXCR.2017.03.046.
Mitov, Mihail I., E-mail: m.mitov@uky.edu, Harris, Jennifer W., Alstott, Michael C., Zaytseva, Yekaterina Y., Evers, B. Mark, Department of Surgery, University of Kentucky, Lexington, KY 40506, Butterfield, D. Allan, and Department of Chemistry, University of Kentucky, Lexington, KY 40506. Mon . "Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines". United States. doi:10.1016/J.YEXCR.2017.03.046.
@article{osti_22649856,
title = {Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines},
author = {Mitov, Mihail I., E-mail: m.mitov@uky.edu and Harris, Jennifer W. and Alstott, Michael C. and Zaytseva, Yekaterina Y. and Evers, B. Mark and Department of Surgery, University of Kentucky, Lexington, KY 40506 and Butterfield, D. Allan and Department of Chemistry, University of Kentucky, Lexington, KY 40506},
abstractNote = {Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, microplate based, label-free detection approach. This study investigates how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32 °C, 37 °C and 42 °C using assay medium conditions and equipment settings adjusted to produce equal oxygen and pH levels ubiquitously at the beginning of all experiments. The results suggest that temperature significantly changes multiple components of glycolytic and mitochondrial function of all cell lines tested. Under hypothermia conditions (32 °C), the extracellular acidification rates (ECAR) of CRC cells were significantly lower compared to the same basal ECAR levels measured at 37 °C. Mitochondrial stress test for SW480 cells at 37 °C vs 42 °C demonstrated increased proton leak while all other OCR components remained unchanged (similar results were detected also for the patient-derived xenograft cells Pt.93). Interestingly, the FCCP dose response at 37 °C vs 42 °C show significant shifts in profiles, suggesting that single dose FCCP experiments might not be sufficient to characterize the mitochondrial metabolic potential when comparing groups, conditions or treatments. These findings provide valuable insights for the metabolic and bioenergetic changes of CRC cells under hypo- and hyperthermia conditions that could potentially lead to development of better targeted and personalized strategies for patients undergoing combined thermotherapy with chemotherapy.},
doi = {10.1016/J.YEXCR.2017.03.046},
journal = {Experimental Cell Research},
number = 2,
volume = 354,
place = {United States},
year = {Mon May 15 00:00:00 EDT 2017},
month = {Mon May 15 00:00:00 EDT 2017}
}