Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation

• Published in: Journal of pathology and translational medicine 2023, 57(6), , pp.305-314
• Main Authors: Shin, Jun Sang, Kim, Tae-Gyu, Kim, Young Hwa, Eom, So Yeong, Park, So Hyun, Lee, Dong Hyun, Park, Tae Jun, Park, Soon Sang, Kim, Jang-Hee
• Format: Article
• Language: English
• Subjects: Cell cycle; cellular senescence; Colorectal cancer; colorectal neoplasms; Dehydrogenases; Enzymes; Hydrogen peroxide; Metabolism; Metabolites; nadh; oxidative phosphorylation; Phosphorylation; Potassium; Scanners; Senescence; 병리학
• ISSN: 2383-7837; 2383-7845
• DOI: 10.4132/jptm.2023.10.09

Background: Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.Methods: Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.Results: Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.Conclusions: Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.