Discovery of a Ruthenium Complex for the Theranosis of Glioma through Targeting the Mitochondrial DNA with Bioinformatic Methods

• Published in: International journal of molecular sciences Vol. 20; no. 18; p. 4643
• Main Authors: Zhang, Le, Fu, Chen, Li, Jin, Zhao, Zizhen, Hou, Yixue, Zhou, Wei, Fu, Ailing
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.09.2019; MDPI
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Binding; Binding sites; Biotechnology; Brain cancer; Cell growth; Cell Line, Tumor; Cell viability; computation docking; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Cytotoxicity; Dehydrogenases; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; DNA, Mitochondrial - metabolism; DNA, Neoplasm - metabolism; Drug Delivery Systems; Endothelial cells; Glioma; Glioma - drug therapy; Glioma - metabolism; Glioma - pathology; Glioma cells; Hepatocytes; Humans; Intermediates; Male; Metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Mitochondrial DNA; mtDNA mutation; Mutation; organometallic complexes; Oxidative phosphorylation; Phosphorylation; Proteins; Ruthenium - chemistry; Ruthenium - pharmacology; Ruthenium compounds; Tricarboxylic acid cycle; Tumors; Umbilical vein; Xenograft Model Antitumor Assays; organometallic complexes; mtDNA mutation; glioma; computation docking
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20184643

Glioma is the most aggressive and lethal brain tumor in humans. Mutations of mitochondrial DNA (mtDNA) are commonly found in tumor cells and are closely associated with tumorigenesis and progress. However, glioma-specific inhibitors that reflect the unique feature of tumor cells are rare. Here we uncover RC-7, a ruthenium complex with strong red fluorescence, could bind with glioma mtDNA and then inhibited the growth of human glioma cells but not that of neuronal cells, liver, or endothelial cells. RC-7 significantly reduced energy production and increased the oxidative stress in the glioma cells. Administration of RC-7 into mice not only could be observed in the glioma mass of brain by fluorescence imaging, but also obviously prevented the growth of xenograft glioma and prolonged mouse survival days. The findings suggested the theranostic application of a novel type of complex through targeting the tumor mtDNA.