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Differential killing and radio-modifying effects of iodoacetate in mammalian normal and cancer cells

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Abstract

To explore possible applications of iodoacetate (IA), a glycolytic inhibitor, in cancer treatment, we screened its cytotoxicity and radioprotective/sensitizing efficacy in three different mammalian cell lines; A549 (human lung carcinoma), MCF7 (human mammary cancer), a non-cancerous CHO (Chinese hamster ovary) cells and human lymphocytes. Experiments were carried out using IA concentrations ranging from 0.01 to 2.5 µg/ml, with or without 60Coγ-radiation. In the outcomes, IA was found to exhibit higher toxicity in the cancer cells, whereas it was non-toxic/marginally toxic to the non-cancerous cells. Considerably higher glucose uptake in both cancer cells lines was observed indicating higher rates of glycolysis. IA significantly inhibited glycolysis as reflected by GAPDH activity inhibition. Radiomodifying effects of IA were found to be concentration dependent in both cancerous and non-cancerous cells. The response in non-cancerous was found to be biphasic: at lower concentrations, it offered significant radioprotection; however, the protection decreased with increasing concentration. Moreover, at the highest tested concentration, marginal radiosensitization was also observed (as indicated by clonogenic assay). In both cancer cells, IA offered significant amount of radiosensitization which was considerably high at higher concentrations. Further experiments were carried out to estimate the Dose Modification Factor (DMF) to quantify and compare relative radiosensitization by IA in cancer and normal cell lines. The DMF was calculated for three different concentrations of IA, 0.5, 1, and 1.5 µg/ml, and corresponding values were found to be 1.26, 1.43, and 1.89 for A549 cancer cells, whereas for normal CHO cells, it was 1.13, 1.13, and 1.24. In conclusion, differential killing and radiosensitizing effects of IA suggest that it may have potential use as a anticancer agent and radiosensitizer in cancer therapy.

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Acknowledgements

We acknowledge the technical assistance by Mr. Tondlekar P., Mr. Jagtap S. and Mr. Thorat U.B. Flow-cytometry-related assistance was rendered by Mr. Prayag A. We also sincerely acknowledge support and guidance by Dr. Pradeepkumar K.S., Associate Director, HS&E Group, BARC and Mr. D.A.R. Babu, Ex-Head, RP&AD, BARC.

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Authors and Affiliations

  1. Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India

    Usha Yadav, K. B. Anjaria, K. B. Shirsath, Utkarsha N. Desai, Rajesh K. Chaurasia, Nagesh N. Bhat & B. K. Sapra

  2. Department of Studies in Physics, Mangalore University, Mangalore, Karnataka, 574199, India

    Rajesha Nairy

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  1. Usha Yadav
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  2. K. B. Anjaria
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  3. Rajesha Nairy
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  4. K. B. Shirsath
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  5. Utkarsha N. Desai
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  8. B. K. Sapra
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Correspondence to Nagesh N. Bhat.

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Yadav, U., Anjaria, K.B., Nairy, R. et al. Differential killing and radio-modifying effects of iodoacetate in mammalian normal and cancer cells. Radiat Environ Biophys 56, 227–239 (2017). https://doi.org/10.1007/s00411-017-0699-0

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  • DOI: https://doi.org/10.1007/s00411-017-0699-0

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