Song et al., showed that 2-methoxyestradiol increases human MM cell death, by stimulating the production of mitochondrial ROS and raising Ca2+ levels within the cells, due to the increased activation of c-Jun N terminal kinase (JNK) and mitogen-activated protein kinase 4/7 (MKK4/7, 140). This evidence concerns the gene MAP2K4 and Miyoshi myopathy.