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Low daunomycin concentrations protect colorectal cancer cells from hypoxia-induced apoptosis

Oncogene volume 24, pages 1788–1793 (2005)Cite this article

Abstract

Hypoxia, a common feature of solid tumors, is a direct stress that triggers apoptosis in many cell types. Poor or irregular tumor vascularization also leads to a decreased drug diffusion and cancer cells distant from blood vessels (hypoxic cells) are exposed to low drug concentrations. In this report, we show that low daunomycin concentrations protect HCT116 colorectal cancer cells from hypoxia-induced apoptosis. While hypoxia induced p53 accumulation without expression of its responsive genes (bax and p21), daunomycin treatment restored p53 transactivation activity and cell cycle progression. We also demonstrated a role for Akt activation in daunomycin-induced protection through phosphorylation and inactivation of the Bcl-2 family proapoptotic factor Bad. Our data therefore suggest that chemotherapy could possibly, because of low concentrations in poorly vascularized tumors, protect cancer cells from hypoxia-induced cytotoxicity.

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Acknowledgements

We thank Drs Yu and Vogelstein for HCT116 P21−/− cells. C Lechanteur is Senior Research Assistant, V Benoît is Research Assistant, A Chariot and M-P Merville are Research Associates of the National Fund for Scientific Research (Belgium). This research was supported by the ‘Leon Fredericq Foundation’, the ‘Centre Anticancéreux près l’ULg’ (Liège, Belgium), and by the Belgian Federation against Cancer.

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  1. Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrated Genoproteomics, University of Liège, Belgium

    Chantal Lechanteur, Valérie Benoît, Valérie Deregowski, Alain Chariot, Marie-Paule Merville & Vincent Bours

  2. Laboratory of Anatomopathology, Center for Biomedical Integrated Genoproteomics, University of Liège, Belgium

    Nathalie Jacobs & Roland Greimers

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  1. Chantal Lechanteur
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Correspondence to Vincent Bours.

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Lechanteur, C., Jacobs, N., Greimers, R. et al. Low daunomycin concentrations protect colorectal cancer cells from hypoxia-induced apoptosis. Oncogene 24, 1788–1793 (2005). https://doi.org/10.1038/sj.onc.1208436

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