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Fenvalerate (Fen), a synthetic pyrethroid insecticide, is widely used in agricultural, domestic and veterinary applications. Fen induces abnormal cell proliferation and apoptosis, which are linked to its hazardous effects. However, this view is controversial and the underlying molecular mechanisms remain elusive. In the present study, the effects of Fen on cadmium (Cd)-induced apoptosis and the associated molecular mechanisms were investigated in human myeloid leukemia U937 cells. U937 cells were treated with 50 μ m cadmium chloride (CdCl2) with or without Fen pretreatment at 1-50 μ m. Apoptosis was evaluated by externalization of phosphatidylserine on the plasma membrane. The expression levels of apoptosis-related proteins, including Bcl-2 family members were determined by western blot analysis. The results revealed that pretreatment with Fen at 20 μ m for 12 hours significantly inhibited Cd-induced apoptosis. Decreased expression of pro-apoptotic Bcl-2 family proteins (Noxa and Bid) and increased expression of anti-apoptotic proteins (Bcl-xL, Mcl-1 and XIAP) were observed after combined treatment with Fen and CdCl2. Phosphorylation of ERK and AKT was increased, while phosphorylation of JNK was decreased by the combined treatment, compared with CdCl2 treatment alone. In conclusion, Fen decreased apoptotic sensitivity induced by Cd in U937 cells. This effect was associated with activation of ERK and AKT, suppression of JNK and changes in expression of Bcl-2 family proteins and XIAP. The present findings suggest a potential influence of Fen on Cd toxicity via suppression of apoptosis. Fen decreased apoptotic sensitivity induced by Cd, and thus it may contribute carcinogenic risk and influence on cancer therapy. [ABSTRACT FROM AUTHOR]