Redox Imbalance and Biochemical Changes in Cancer by Probing Redox-Sensitive Mitochondrial Cytochromes in Label-Free Visible Resonance Raman Imaging

Abstract

To monitor redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving methods are required. We 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. We 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. We 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.

Double face of cytochrome c in cancers by Raman imaging

“…Small concentration of oxidized cytochrome c (Fe 3+ green colour in Fig. 1 ) was found with a characteristic Raman peaks at 750, 1126, 1582 cm −1 and 1634 cm −1 22 . The oxidized form of cytochrome c (Fe 3+ ) can induce caspase activation in the process of apoptosis, while the reduced form (Fe 2+ ) cannot 23 .…”

“…The altered fluidity of the membranes of epithelial cells leads to mechanical deformations allowing for Cyt c release to lumen of the duct. In this hypothesis the release of Cyt c is a result, not a cause, of malignant transformation due to lipid reprogramming in cancer development 22 , 43 , 44 . To date, no pathway of Cyt c release that results in caspase activation has been compellingly demonstrated in any invertebrate, despite the presence of homologues of many of the molecules that mediate and/or regulate the intrinsic pathway of apoptosis in vertebrate cells.…”

Revision of Commonly Accepted Warburg Mechanism of Cancer Development: Redox-Sensitive Mitochondrial Cytochromes in Breast and Brain Cancers by Raman Imaging

“…To properly address redox state changes of mitochondrial cytochromes in brain and breast cancers by Raman spectroscopy and imaging, we systematically investigated how the Raman method responds to in vitro human cells and ex vivo human tissues [ 26 , 27 ]. In vitro experiments will allow to study a single cell by limiting the cell-to-cell interactions.…”

The effect of COVID-19 mRNA vaccine on human lung carcinoma cells in vitro by means of Raman spectroscopy and imaging

“…It is worth of noticing that a similar effect of lower concentration of cytochrome c we observed in brain cancer cells. We showed that the Raman intensity of the band at 1584 cm −1 corresponding to the concentration of cytochrome c in mitochondria of a single cell in vitro decreases with brain tumor aggressiveness [9,14].…”