Biology subjects

Abramczyk, H.

Publications and source records attributed to Abramczyk, H..

4 recordsLinked to original sources

bioRxiv2021

Revision of commonly accepted Warburg mechanism of cancer development. Redox-sensitive mitochondrial cytochromes in breast and brain cancers by Raman imaging

BackgroundWe studied oncogenic processes that characterize human breast cancer (infiltrating ductal carcinoma (IDC)) and human brain tumors: glioma, astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. MethodsWe used Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues surgically resected specimens of human tissues and in vitro human brain cells of normal astrocytes (NHA), astrocytoma (CRL-1718), glioblastoma (U87-MG) and medulloblastoma (Daoy), and human breast cells of normal cells (MCF 10A), slightly malignant cells (MCF7) and highly aggressive cells (MDA-MB-231) by means of Raman microspectroscopy at 532 nm. ResultsWe visualized localization of cytochromes by Raman imaging in the major organelles in cancer cells. We demonstrated that the "redox state Raman marker" of the ferric low spin heme in cytochrome c at 1584 cm-1 can serve as a sensitive indicator of cancer aggressiveness. We compared concentration of reduced cytochrome c and the grade of cancer aggressiveness in cancer tissues and single cells and specific organelles in cells: nucleous, mitochondrium, lipid droplets, cytoplasm, and membrane. ConclusionsWe found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers in human tissues. Our results suggest that the mechanisms controlling the electron transport chain are spectacularly deregulated in cancers and indicate that electron transport, organized in terms of electronegativity, is inhibited between complex III and cytochrome c for isolated cells in vitro and between cytochrome c and complex IV in brain and breast tissues. The results provide evidence that the extracellular matrix and interactions with cell microenvironment play an important role in the mechanisms controlling the electron transport chain by cytochrome c. Our results reveal the universality of Raman vibrational characteristics of mitochondrial cytochromes in metabolic regulation in cancers that arise from epithelial breast cells and brain glial cells.

cancer biology↗

bioRxiv2020

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

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

cancer biology↗

bioRxiv2020

Redox state changes of mitochondrial cytochromes in brain and breast cancers by Raman spectroscopy and imaging

This paper presents a non-invasive approach to study redox status of cytochromes in vitro human brain cells of normal astrocytes (NHA), astrocytoma (CRL-1718), glioblastoma (U87- MG) and medulloblastoma (Daoy), and human breast cells of normal cells (MCF10A), slightly malignant cells (MCF7) and highly aggressive cells (MDA-MB-231), in vivo animal models, and ex vivo brain and breast tissues surgically resected human specimens by means of Raman microspectroscopy at 355 nm, 532 nm, 785 nm and endospectroscopic Raman probe at 785 nm. Here we show that the amount of reduced cytochrome becomes abnormally high in human brain tumors and breast cancers. In contrast, the amount of reduced cytochrome c is lower in cancer cells when compared to the normal one at in vitro conditions when the effect of microenvironment is eliminated. Mitochondrial dysfunction and alterations in the chemical composition of the nucleus, mitochondria, lipid droplets, cytoplasm in single cells have been detected by Raman imaging. Incubation in vitro with retinoic acid increases the amount of reduced cytochrome c.

cancer biology↗

bioRxiv2020

Novel strategies of Raman imaging for monitoring intracellular retinoid metabolism in cancer cells

We developed a label-free Raman method for whole-cell biochemical imaging to detect molecular processes that occur in normal and cancer brain cells due to retinol transport in human cancers at the level of isolated organelles. Our approach allows to create biochemical maps of retinoids localization in lipid droplets, mitochondria and nuclei in single cells. The maps were capable of discriminating triglycerides (TAG) from retinoids (RE) in lipid droplets (LD), and mitochondria providing an excellent tool to monitor intracellular retinoid metabolism. We detected spectral changes that arose in proteins and lipids due to retinoid metabolism in human cell lines of normal astrocytes and high-grade cancer cells of glioblastoma as well as in human medulloblastoma and glioblastoma tissue. Raman imaging is an effective tool for monitoring retinoids and retinol binding proteins involved in carcinogenesis by detecting unique spectral signatures of vibrations. We found two functionally distinct lipid droplets: TAG-LD, for energy storage, and RE-LD, for regulating mechanisms of signal transduction. Raman polarization measurements revealed the occurrence of conformational changes affecting discrete regions of proteins associated with retinol binding. Aberrant expression of retinoids and retinol binding proteins in human tumours were localized in lipid droplets, and mitochondria.

cancer biology↗