Transformation of nomifensine using ionizing radiation and exploration of its anticancer effects in MCF-7 cells

Breast Cancer is one of the most challenging diseases to treat in humans worldwide. There are several alternatives in treating this life-threatening disease; however, chemoresistance is probably the biggest obstacle to the treatment of breast Cancer. It may be essential to develop a therapeutic candidate material with less reversible effects and high treatment efficiency to solve this problem. The present study applied an ionizing radiation approach employing nomifensine (NF) to transform its chemical characteristics and investigated its potential to kill human breast Cancer cells (MCF-7). Irradiated (IR-) NF was analyzed using high-performance liquid chromatography. The findings showed that NF inhibited the proliferation of breast Cancer cells and increased the rate of Apoptosis. In addition, IR-NF induced the accumulation of cytosolic Reactive Oxygen Species and enhanced mitochondrial aggregation. Additionally, mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH 2-terminal kinase) were involved in damage signaling induced by IR-NF and IR-NF suppressed β-catenin nuclear translocation. It is suggested that irradiation can be an effective method to maximize the efficacy of existing drugs and that IR-NF has the potential to be a drug candidate for treating patients with breast Cancer.

breast cancer; mitogen-activated protein kinase; nomifensine; radiolytic transformation; β-catenin.