Direct evidence of mitochondrial G-quadruplex DNA by using fluorescent anti-cancer agents.
Bottom Line: In this paper, we provide the first evidence supporting the presence of G4 in the mitochondrial DNA (mtDNA) of live cells.In this study, we use fluorescence lifetime imaging microscopy to verify the existence of mtDNA G4s in live cells.Bioactivity studies indicate that interactions between these anti-cancer agents and mtDNA G4 can suppress mitochondrial gene expression.
Affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan.Show MeSH
Related in: MedlinePlus
Mentions: o-BMVC is a G4 ligand with no appreciable cytotoxic effects on cancer cells. However, the BMVC derivative, BMVC-12C-P, is a fluorescent anti-cancer agent. The strong fluorescence of BMVC-12C-P accumulates primarily in the mitochondria of HeLa cancer cells, whereas weak fluorescence is distributed in the cytoplasm of MRC-5 normal fibroblasts (Figure 2A). Variations in the intensity of BMVC-12C-P fluorescence between cancer and normal cells were further confirmed using flow cytometry (Figure 2B). These variations can be attributed to a significant increase in the fluorescence of BMVC-12C-P upon interacting with DNA (Supplementary Figure S1) and also to a greater accumulation of BMVC-12C-P in the mitochondria of cancer cells than in normal cells.
Affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan.