A novel radiolytic rotenone derivative, rotenoisin A, displays potent anticarcinogenic activity in breast cancer cells.
Chemotherapy for cancer treatment has therapeutic limitations, such as drug resistance, excessive toxic effects and undesirable adverse effects. Therefore, efforts to improve the safety and efficacy of chemotherapeutic agents are essential. Ionizing radiation can improve physiological and pharmacological properties by transforming structural modifications of the drug. In this study, in order to reduce the adverse effects of rotenone and increase anticancer activity, a new radiolytic rotenone derivative called rotenoisin A was generated through radiolytic transformation. Our findings showed that rotenoisin A inhibited the proliferation of breast cancer cells and increased the rate of apoptosis, whereas it had no inhibitory effect on primary epidermal keratinocytes compared with rotenone. Moreover, rotenoisin A-induced DNA damage by increasing reactive oxygen species (ROS) accumulation. It was also confirmed not only to alter the composition ratio of mitochondrial proteins, but also to result in structural and functional changes. The anticancer effect and molecular signalling mechanisms of rotenoisin A were consistent with those of rotenone, as previously reported. Our study suggests that radiolytic transformation of highly toxic compounds may be an alternative strategy for maintaining anticancer effects and reducing the toxicity of the parent compound.
['Bak|Dong-Ho|DH|', 'Kang|Seong Hee|SH|', 'Park|Chul-Hong|CH|', 'Chung|Byung Yeoup|BY|', 'Bai|Hyoung-Woo|HW|']
D000970:Antineoplastic Agents D001943:Breast Neoplasms D016923:Cell Death D049109:Cell Proliferation D004249:DNA Damage D005260:Female D006801:Humans D020935:MAP Kinase Signaling System D061986:MCF-7 Cells D024101:Mitochondrial Proteins D010766:Phosphorylation D017382:Reactive Oxygen Species D012402:Rotenone D051028:bcl-2-Associated X Protein
rotenone rotenoisin A breast cancer radiolytic transformation mitogen-activated protein kinase (MAPK)