Disruption of mitochondrial function augments the radiosensitivity of prostate cancer cell lines.

Autor:	Adamczuk GM; Medical University, Lublin, Poland.; Independent Medical Biology Unit, Lublin, Poland., Humeniuk E; Medical University, Lublin, Poland.; Independent Medical Biology Unit, Lublin, Poland., Adamczuk K; Medical University, Lublin, Poland.; Department of Biochemistry and Molecular Biology, Medical University, Lublin, Poland., Madej-Czerwonka B; Medical University, Lublin, Poland.; Human Anatomy Department, Medical University, Lublin, Poland., Dudka J; Medical University, Lublin, Poland.; Department of Toxicology, Medical University, Lublin, Poland.
Jazyk:	angličtina
Zdroj:	Annals of agricultural and environmental medicine : AAEM [Ann Agric Environ Med] 2023 Mar 31; Vol. 30 (1), pp. 65-76. Date of Electronic Publication: 2022 Oct 21.
DOI:	10.26444/aaem/155382
Abstrakt:	Introduction: Ionizing radiation is one of the most widely used therapeutic methods in the treatment of prostate cancer, but the problem is developing radioresistance of the tumour. There is evidence that metabolic reprogramming in cancer is one of the major contributors to radioresistance and mitochondria play a crucial role in this process. Objective: The aim of the study was to assess the influence of oxidative phosphorylation uncoupling to radiosensitivity of prostate cancer cells differing in metabolic phenotype. Material and Methods: LNCaP, PC-3 and DU-145 cells were exposed to X-rays and simultaneously treated with 2,4-dinitrophenol (2,4-DNP). The radiosensitive of cell lines was determined by cell clonogenic assay and cell cycle analysis. The cytotoxic effect was evaluated with MTT and CVS (Crystal violet staining) assay, apoptosis detection and cell cycle analysis. The phenotype of the cells was determined by glucose uptake and lactate release, ATP level measurement as well as basal reactive oxygen species level and mRNA expression of genes related to oxidative stress defence. Results: The synergistic effect of 2,4-dinitrophenol and X-ray was observed only in the case of the LNCaP cell line. Conclusions: Phenotypic analysis indicates that this may be due to the highest dependence of these cells on oxidative phosphorylation and sensitivity to disruption of their redox status.
Databáze:	MEDLINE
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