Research Division for Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup-si, Jeollabuk-do, Republic of Korea.
Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
J Radiat Res. 2021 Mar 10;62(2):249-258. doi: 10.1093/jrr/rrab005.
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.
癌症治疗的化疗具有治疗局限性，如耐药性、过度的毒性作用和不良的副作用。因此，努力提高化疗药物的安全性和疗效至关重要。电离辐射可以通过改变药物的结构修饰来改善生理和药理特性。在这项研究中，为了降低鱼藤酮的不良反应并提高抗癌活性，通过放射转化生成了一种新的鱼藤酮衍生物，称为鱼藤异噁唑 A。我们的研究结果表明，鱼藤异噁唑 A 抑制乳腺癌细胞的增殖并增加细胞凋亡率，而与鱼藤酮相比，其对原代表皮角质形成细胞没有抑制作用。此外，鱼藤异噁唑 A 通过增加活性氧 (ROS) 积累来诱导 DNA 损伤。还证实它不仅改变了线粒体蛋白的组成比例，而且导致结构和功能发生变化。鱼藤异噁唑 A 的抗癌作用和分子信号机制与先前报道的鱼藤酮一致。我们的研究表明，高毒性化合物的放射转化可能是维持抗癌效果和降低母体化合物毒性的一种替代策略。
