Benzo(a)pyrene affects proliferation with reference to metabolic genes and ROS/HIF-1α/HO-1 signaling in A549 and MCF-7 cancer cells.

Benzo(a)pyrene (BaP) is a representative polycyclic aromatic hydrocarbon (PAH) compound, which has been implicated in cancer initiation and promotion. Although BaP is one of the most extensively studied pollutants, the underlying mechanisms through which BaP affects reactive oxygen species (ROS)/hypoxia-inducible factor 1α (HIF-1α)/heme oxygenase 1(HO-1) signaling during lung or breast carcinogenesis are not yet fully understood. In this study, we analyzed the effects of 0 (control), 1, 5, or 25 µM BaP exposure on A549 and MCF-7 cancer cells, by evaluating cell viability, cell cycle, and regulatory protein expression, metabolic gene expression, and ROS/HIF-1α/HO-1 signaling. Cell viability increased following exposure to 1 and 5 µM BaP in A549 cells but decreased following exposure to all concentrations of BaP in MCF-7 cells. BaP significantly increased the proportions of cells in S and G2/M phases, with concomitant reductions in the proportions of cells in G0/G1 phase, following 5 and 25 µM exposure, which was accompanied by the upregulation of the regulatory proteins cyclin A, cyclin B, cyclin-dependent kinase (CDK)1, and CDK2. The subsequent upregulation of cytochrome p450 (CYP)1A1, CYP1B1, CYP3A4, epoxide hydrolase (EH), aldo-keto reductase (AKRC1) expression, and the attenuation of multi-drug resistance protein 4 (MRP4), glutathione-S-transferase (GST)1A1, and GST1B1 were also observed in both cell lines. Moreover, the induction of ROS and the modulation of HIF-1α and HO-1 were observed after BaP exposure. Taken together, these findings suggest that BaP affects proliferation with reference to metabolic genes and ROS/HIF-1α/HO-1 signaling in A549 and MCF-7 cancer cells.