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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Article info
Publication history
Accepted:
March 21,
2007
Identification
Copyright
© 2007 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
