Thermal sensitization through ROS modulation: A strategy to improve the efficacy of hyperthermic intraperitoneal chemotherapy

Chia Chi Wang, Fei Chen, Eugene Kim, Lawrence Harrison

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: The purpose of this study was to investigate whether modulation of cellular reactive oxygen species (ROS) provides a synergistic effect with hyperthermia to induce tumor cell death in a colon cancer cell line. Materials and Methods: HT-29 colon cancer cells were exposed to heat (43°C) in the presence of the ROS-generating drug, 2-2′-azobis-(2-amidinopropane) dihydrochloride (AAPH) for 1 h. Viable cell mass and apoptosis was measured by MTT and annexin V staining, respectively. Oxidative stress was evaluated by DCFH fluorescence. Protein levels were determined by Western blot analysis. Results: A synergistic effect on cell viability with AAPH was noted under hyperthermic conditions as compared with hyperthermia alone (P < .05). The number of nonviable cells after hyperthermia and AAPH exposure was also significantly increased compared with AAPH at 37°C (42% vs 20%, P < .05). ROS levels were increased modestly with AAPH at 37°C, whereas they increased significantly in a dose-dependent manner with AAPH at 43°C. Transient increases of phosphorylated-p38 and ERK and decreases in phosphorylated-AKT were observed in the cells exposed to AAPH at 43°C. Pretreatment of inhibitors of p38 yielded additional decreases in cell mass when used in combination with AAPH and hyperthermia (P < .05). Increased expression of HSP 27 observed at 43°C was abrogated with AAPH exposure. Conclusions: Oxidative stress increased the cytotoxic effects of hyperthermia in colon cancer cells. Thermal sensitization through modulation of cellular ROS may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

Original languageEnglish (US)
Pages (from-to)384-392
Number of pages9
JournalSurgery
Volume142
Issue number3
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

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Reactive Oxygen Species
Hot Temperature
Drug Therapy
Fever
Colonic Neoplasms
Oxidative Stress
2,2'-azobis(2-amidinopropane)
Annexin A5
Cell Survival
Cell Death
Cell Count
Fluorescence
Western Blotting
Apoptosis
Staining and Labeling
Cell Line
Pharmaceutical Preparations
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

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title = "Thermal sensitization through ROS modulation: A strategy to improve the efficacy of hyperthermic intraperitoneal chemotherapy",
abstract = "Background: The purpose of this study was to investigate whether modulation of cellular reactive oxygen species (ROS) provides a synergistic effect with hyperthermia to induce tumor cell death in a colon cancer cell line. Materials and Methods: HT-29 colon cancer cells were exposed to heat (43°C) in the presence of the ROS-generating drug, 2-2′-azobis-(2-amidinopropane) dihydrochloride (AAPH) for 1 h. Viable cell mass and apoptosis was measured by MTT and annexin V staining, respectively. Oxidative stress was evaluated by DCFH fluorescence. Protein levels were determined by Western blot analysis. Results: A synergistic effect on cell viability with AAPH was noted under hyperthermic conditions as compared with hyperthermia alone (P < .05). The number of nonviable cells after hyperthermia and AAPH exposure was also significantly increased compared with AAPH at 37°C (42{\%} vs 20{\%}, P < .05). ROS levels were increased modestly with AAPH at 37°C, whereas they increased significantly in a dose-dependent manner with AAPH at 43°C. Transient increases of phosphorylated-p38 and ERK and decreases in phosphorylated-AKT were observed in the cells exposed to AAPH at 43°C. Pretreatment of inhibitors of p38 yielded additional decreases in cell mass when used in combination with AAPH and hyperthermia (P < .05). Increased expression of HSP 27 observed at 43°C was abrogated with AAPH exposure. Conclusions: Oxidative stress increased the cytotoxic effects of hyperthermia in colon cancer cells. Thermal sensitization through modulation of cellular ROS may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.",
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Thermal sensitization through ROS modulation : A strategy to improve the efficacy of hyperthermic intraperitoneal chemotherapy. / Wang, Chia Chi; Chen, Fei; Kim, Eugene; Harrison, Lawrence.

In: Surgery, Vol. 142, No. 3, 01.09.2007, p. 384-392.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thermal sensitization through ROS modulation

T2 - A strategy to improve the efficacy of hyperthermic intraperitoneal chemotherapy

AU - Wang, Chia Chi

AU - Chen, Fei

AU - Kim, Eugene

AU - Harrison, Lawrence

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Background: The purpose of this study was to investigate whether modulation of cellular reactive oxygen species (ROS) provides a synergistic effect with hyperthermia to induce tumor cell death in a colon cancer cell line. Materials and Methods: HT-29 colon cancer cells were exposed to heat (43°C) in the presence of the ROS-generating drug, 2-2′-azobis-(2-amidinopropane) dihydrochloride (AAPH) for 1 h. Viable cell mass and apoptosis was measured by MTT and annexin V staining, respectively. Oxidative stress was evaluated by DCFH fluorescence. Protein levels were determined by Western blot analysis. Results: A synergistic effect on cell viability with AAPH was noted under hyperthermic conditions as compared with hyperthermia alone (P < .05). The number of nonviable cells after hyperthermia and AAPH exposure was also significantly increased compared with AAPH at 37°C (42% vs 20%, P < .05). ROS levels were increased modestly with AAPH at 37°C, whereas they increased significantly in a dose-dependent manner with AAPH at 43°C. Transient increases of phosphorylated-p38 and ERK and decreases in phosphorylated-AKT were observed in the cells exposed to AAPH at 43°C. Pretreatment of inhibitors of p38 yielded additional decreases in cell mass when used in combination with AAPH and hyperthermia (P < .05). Increased expression of HSP 27 observed at 43°C was abrogated with AAPH exposure. Conclusions: Oxidative stress increased the cytotoxic effects of hyperthermia in colon cancer cells. Thermal sensitization through modulation of cellular ROS 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 modulation of cellular reactive oxygen species (ROS) provides a synergistic effect with hyperthermia to induce tumor cell death in a colon cancer cell line. Materials and Methods: HT-29 colon cancer cells were exposed to heat (43°C) in the presence of the ROS-generating drug, 2-2′-azobis-(2-amidinopropane) dihydrochloride (AAPH) for 1 h. Viable cell mass and apoptosis was measured by MTT and annexin V staining, respectively. Oxidative stress was evaluated by DCFH fluorescence. Protein levels were determined by Western blot analysis. Results: A synergistic effect on cell viability with AAPH was noted under hyperthermic conditions as compared with hyperthermia alone (P < .05). The number of nonviable cells after hyperthermia and AAPH exposure was also significantly increased compared with AAPH at 37°C (42% vs 20%, P < .05). ROS levels were increased modestly with AAPH at 37°C, whereas they increased significantly in a dose-dependent manner with AAPH at 43°C. Transient increases of phosphorylated-p38 and ERK and decreases in phosphorylated-AKT were observed in the cells exposed to AAPH at 43°C. Pretreatment of inhibitors of p38 yielded additional decreases in cell mass when used in combination with AAPH and hyperthermia (P < .05). Increased expression of HSP 27 observed at 43°C was abrogated with AAPH exposure. Conclusions: Oxidative stress increased the cytotoxic effects of hyperthermia in colon cancer cells. Thermal sensitization through modulation of cellular ROS may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

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JO - Surgery

JF - Surgery

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