Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Molecules. 2023 Mar 16;28(6):2690. doi: 10.3390/molecules28062690.
Mitochondria have a crucial role in regulating energy metabolism and their dysfunction has been linked to tumorigenesis. Cancer diagnosis and intervention have a great interest in the development of new agents that target biomolecules within mitochondria. However, monitoring and modulating mitochondria RNA (mtRNA), an essential component in mitochondria, in cells is challenging due to limited functional research and the absence of targeting agents. In this study, we designed and synthesized a fluorescent quinolinium derivative, , which actively lit up with mtRNA in both normal and cancer cells in vitro. Additionally, we evaluated the function of as an mtRNA ligand and found that it effectively induced severe mitochondrial dysfunction and OXPHOS inhibition in RKO colorectal cancer cells. Treatment with resulted in apoptosis, cell cycle blockage at the G2/M phase, and the effective inhibition of cell proliferation. Our findings suggest that has great potential as a promising probe and therapeutic agent for mtRNA, with the potential for treating colorectal cancer.
线粒体在调节能量代谢方面起着至关重要的作用，其功能障碍与肿瘤发生有关。癌症的诊断和干预非常关注开发针对线粒体内部生物分子的新药物。然而，由于功能研究有限且缺乏靶向药物，监测和调节线粒体 RNA（mtRNA）——线粒体的一个重要组成部分，在细胞中是具有挑战性的。在这项研究中，我们设计并合成了一种荧光喹啉鎓衍生物 ，该衍生物在体外的正常细胞和癌细胞中都能与 mtRNA 积极结合。此外，我们评估了 作为 mtRNA 配体的功能，发现它能有效地诱导 RKO 结直肠癌细胞中严重的线粒体功能障碍和 OXPHOS 抑制。用 处理会导致细胞凋亡、细胞周期阻滞在 G2/M 期，并有效抑制细胞增殖。我们的研究结果表明， 作为 mtRNA 的一种很有前途的探针和治疗剂具有很大的潜力，有可能用于治疗结直肠癌。
