Abstract
Using time-gated fluorescence lifetime imaging microscopy, significantly more signals from 3,6-bis(1-methyl-2-vinyl-pyridinium) carbazole diiodide (o-BMVC) foci, characterized by the longer fluorescent decay time of o-BMVC, were detected in six types of cancer cells than in three types of normal cells. Accumulating evidence suggested that the o-BMVC foci are mainly the G-quadruplex foci. The large contrast in the number of o-BMVC foci can be considered as a common signature to distinguish cancer cells from normal cells. Further study of tissue biopsy showed that the o-BMVC test provides a high accuracy for clinical detection of head and neck cancers.
Highlights
Cancer remains as one of the leading causes of death in many countries
The results showed that the decay times of o-BMVC are longer upon interaction with 20 G4s than with 10 sequences of duplex and single stranded DNA (Fig. 1b)
It is likely that the large contrast in the number of G4 foci between cancer cells and normal cells may act as a common biomarker for human cancers
Summary
Cancer remains as one of the leading causes of death in many countries. Since early diagnosis can improve the survival of cancer patient, the early detection of cancer has been an unmet and urgent medical need. Biffi et al.[9] have used a fluorescently labeled G4-specific antibody (BG4) to visualize the G4 foci in both cancer and normal cells. Hansel-Hertsch et al.[6] found that immortalized keratinocytes (HaCaT) showed ~4-fold more G4 foci than do normal human epidermal keratinocytes (NHEK) using BG4 immunofluorescence microscopy. It appears that the difference in G4 foci between cancer cells and normal cells warrants further study. Of importance is that fluorescence lifetime imaging microscopy (FLIM) showed longer fluorescent decay times of o-BMVC upon interaction with most G4s formed by G-rich sequences in telomeres and some promoter oncogenes (≥2.4 ns) than with other structures such as linear duplexes and hairpin structures (~1.2 ns)[14]. The finding of many more numbers of o-BMVC foci in the nuclei of six cancer cell lines than three normal cell lines prompted us to validate these findings in clinical samples
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