1. ¹Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrated Genoproteomics, University of Liège, Belgium
2. ²Laboratory of Anatomopathology, Center for Biomedical Integrated Genoproteomics, University of Liège, Belgium

Correspondence: V Bours, Laboratory of Medical Chemistry and Human Genetics, CHU B35, Sart Tilman, 4000 Liège, Belgium. E-mail: vbours@ulg.ac.be

Received 24 August 2004; Revised 25 October 2004; Accepted 7 December 2004; Published online 31 January 2005.

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.