Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27

Fei Chen, Reza Rezavi, Cha Chi Wang, Lawrence E. Harrison

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

Original languageEnglish (US)
Pages (from-to)98-103
Number of pages6
JournalOncology
Volume73
Issue number1-2
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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HSP27 Heat-Shock Proteins
Proteasome Endopeptidase Complex
Colonic Neoplasms
Fever
Cell Death
Hot Temperature
Apoptosis
Annexin A5
Small Interfering RNA
Cell Survival
Western Blotting
Staining and Labeling
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27",
abstract = "Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.",
author = "Fei Chen and Reza Rezavi and Wang, {Cha Chi} and Harrison, {Lawrence E.}",
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Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27. / Chen, Fei; Rezavi, Reza; Wang, Cha Chi; Harrison, Lawrence E.

In: Oncology, Vol. 73, No. 1-2, 01.03.2008, p. 98-103.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27

AU - Chen, Fei

AU - Rezavi, Reza

AU - Wang, Cha Chi

AU - Harrison, Lawrence E.

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N2 - Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

AB - Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

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