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 language | English (US) |
|---|---|
| Pages (from-to) | 384-392 |
| Number of pages | 9 |
| Journal | Surgery |
| Volume | 142 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2007 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Surgery
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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 journal › Article
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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U2 - 10.1016/j.surg.2007.03.013
DO - 10.1016/j.surg.2007.03.013
M3 - Article
VL - 142
SP - 384
EP - 392
JO - Surgery
JF - Surgery
SN - 0039-6060
IS - 3
ER -