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The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat cells to chemotherapy agents

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Abstract

Chemotherapy agents initiate tumour cell apoptosis and this is thought to involve oxidative stress. In this study we have investigated the effect of the important antioxidant Vitamin C (ascorbate) on the response of HL60 and Jurkat cells to three chemotherapy drugs, namely etoposide, melphalan and arsenic trioxide (As2O3). Cells grown in routine culture media are deficient in ascorbate and to determine its effect on chemotherapy drug-induced apoptosis we supplemented the cells prior to drug exposure. We found that ascorbate had a varied effect on apoptosis and cell cycle progression. Etoposide-induced apoptosis in HL60 cells was significantly increased in ascorbate-loaded cells as measured by caspase-3 activation and DNA degradation, and this appeared to reflect a decrease in the number of necrotic cells rather than increased cytotoxicity. In contrast, ascorbate had no effect on etoposide-induced apoptosis in Jurkat cells. In both cell types melphalan-induced apoptosis was unaffected by intracellular ascorbate, whereas both apoptosis and growth arrest with low concentrations of As2O3 were diminished. These results indicate that intracellular ascorbate can affect cell responses to chemotherapy drugs in a complex and somewhat unpredictable manner and that it may play an important role in the responsiveness of tumour cells to chemotherapy regimes.

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  1. Trushar Patel

    Present address: New York University School of Medicine, Fifth Avenue, New York, NY, USA

Authors and Affiliations

  1. Free Radical Research Group, Pathology Department, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand

    Prachee Gokhalé, Trushar Patel, Mary J. Morrison & Margret C. M. Vissers

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  1. Prachee Gokhalé
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  2. Trushar Patel
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  4. Margret C. M. Vissers
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Correspondence to Margret C. M. Vissers.

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This study was supported by the Health Research Council of New Zealand.

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Gokhalé, P., Patel, T., Morrison, M.J. et al. The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat cells to chemotherapy agents. Apoptosis 11, 1737–1746 (2006). https://doi.org/10.1007/s10495-006-9787-3

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