Hyperthermia in combination with oxidative stress induces autophagic cell death in HT-29 colon cancer cells

Authors

  • Fei Chen,

    1. Department of Surgery, Division of Surgical Oncology, UMDNJ—New Jersey Medical School, 185 South Orange Avenue, MSB G524, Newark, NJ 07103, USA
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  • Chia-Chi Wang,

    1. Department of Surgery, Division of Surgical Oncology, UMDNJ—New Jersey Medical School, 185 South Orange Avenue, MSB G524, Newark, NJ 07103, USA
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  • Eugene Kim,

    1. Department of Surgery, Division of Surgical Oncology, UMDNJ—New Jersey Medical School, 185 South Orange Avenue, MSB G524, Newark, NJ 07103, USA
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  • Lawrence E. Harrison

    Corresponding author
    1. Department of Surgery, Division of Surgical Oncology, UMDNJ—New Jersey Medical School, 185 South Orange Avenue, MSB G524, Newark, NJ 07103, USA
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Corresponding author. Tel.: +1 973 972 5583; fax: +1 973 972 3730. L.Harrison@UMDNJ.edu

Abstract

The purpose of this study was to evaluate the mechanism of ROS-induced hyperthermic cell death in a colon cancer cell line. HT-29 colon cancer cells were exposed to heat (43 °C) in the presence of tert-butyl hydroperoxide (t-BOOH). t-BOOH combined with hyperthermia significantly decreased cell viability as compared with t-BOOH or hyperthermia alone. This decrease in cell numbers was associated with retardation in the S phase transit and not through apoptosis. Cell death was noted to be accompanied by specific features characteristic of autophagy: the presence of cytoplasmic autophagic vacuoles; autophagosome membrane association of microtubule-associated protein light chain 3; accumulation of acidic vesicular organelles; and increased incorporation of MDC in the autophagosome. 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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