Redox Imbalance and Biochemical Changes in Cancer by probing redox-sensitive mitochondrial cytochromes in label-free visible resonance Raman imaging

Abstract

BackgroundTo monitoring redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving novel methods are required. MethodsWe used Raman spectroscopy and Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues at 532 nm, 633 nm, 785 nm. ResultsWe identified the oncogenic processes that characterize human infiltrating ductal carcinoma (IDC) and human brain tumors: gliomas; astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. We visualized localization of cytochromes by Raman imaging in the breast and brain tissues and analyzed cytochrome c vibrations at 750, 1126, 1337 and 1584 cm-1 as a function of malignancy grade. We found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers and correlates with the grade of cancer aggressiveness. ConclusionsWe showed that Raman imaging provides additional insight into the biology of astrocytomas and breast ductal invasive cancer, which can be used for noninvasive grading, differential diagnosis, delineation of tumor extent, planning of surgery, and radiotherapy and post-treatment monitoring. Simple SummaryGliomas comprise around 30% of human brain tumors, while invasive ductal carcinoma (IDC) comprises around 80% of human breast cancers. The aim of our study was to show that cancerogenesis affects the redox status of mitochondrial cytochromes, which can be tracked by using Raman spectroscopy and imaging. We have shown the correlation between the intensity of cytochromes Raman bands at 750, 1126, 1337 and 1584 cm-1 and malignancy grade for brain and breast cancers. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/409359v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1b5ab1corg.highwire.dtl.DTLVardef@1f4df05org.highwire.dtl.DTLVardef@15dce93org.highwire.dtl.DTLVardef@1a522ee_HPS_FORMAT_FIGEXP M_FIG C_FIG