Chronic exposure of cells to Cr(VI) causes ROS generation which is responsible for malignant cell transformation. Once the cells are malignant transformed, those cells exhibit activated PI3K/Akt, reduced ROS generation, and elevated levels of antioxidants and HIF-1α, resulting in reduction of mitochondrial oxidative phosphorylation and upregulations of pentose phosphate pathway, glycolysis, and glutaminolysis, leading to tumorigenesis.