Effect of hypoxia on chemotherapeutic agents-induced cell death.

HepG2, A549, U2OS, MDA-MB231, HT-29, Hep3B and PC-3 cells were incubated under normoxia (N, 21% O2) or hypoxia (H, 1% O2) in the absence (control) or presence of etoposide, methotrexate, paclitaxel, cisplatin or camptothecin. Apoptosis was assayed by measuring caspase-3/7 activity (Ap) and overall cell death was assessed by measuring LDH release (CD) after 16 or 40 hour incubation respectively. Caspase-3/7 activity was assayed by measuring the fluorescence of free AFC released from the cleavage of the caspase-3/7 specific substrate Ac-DEVD-AFC. The p53 status of each cell line is specified in the second column: wild type (wt), mutated or null. The concentrations used for each molecule on each cell type are indicated. “weak death” means that some cell death (statistically different from the control) is sometimes observed but not reproducible. A light grey cell indicates that hypoxia decreases drug-induced cell death; a dark grey cell indicates that hypoxia does not modify drug-induced cell death; and a black cell indicates that hypoxia aggravates drug-induced cell death. hypoxia protect against cell death; hypoxia has no effect on cell death; hypoxia aggravates cell death.