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- Title
Proline oxidase silencing inhibits p53-dependent apoptosis in MCF-7 breast cancer cells.
- Authors
Oscilowska, Ilona; Huynh, Thi Y. L.; Baszanowska, Weronika; Prokop, Izabela; Surazynski, Arkadiusz; Galli, Mauro; Zabielski, Piotr; Palka, Jerzy
- Abstract
Proline oxidase (POX) is mitochondrial proline-degrading enzyme of dual apoptosis/survival function. POX expression and proline availability are considered an underlying mechanism for differential POX functions. The mechanism for POX-dependent regulation of cell death/survival was studied in wild-type (MCF-7WT) and shRNA POX-silenced breast cancer cells (MCF-7iPOX). Proline concentration and proteomic analyses were determined by LC/MS/QTOF and LC/MS/ORBITRA, respectively. Inhibition of collagen biosynthesis (proline utilizing process) by 2-methoxyestradiol (2ME) contributed to induction of apoptosis in MCF-7WT cells, as detected by increase in the expression of active caspase-3, -9 and p53. The process was not shown in MCF-7iPOX. In MCF-7iPOX cells prolidase activity and expression as well as proline concentration were drastically increased, compared to MCF-7WT cells. Down-regulation of p53 in MCF-7iPOX cells was corroborated by proteomic analysis showing decrease in the expression of p53-related proteins. The mechanism for down-regulation of p53 expression in MCF-7iPOX cells was found at the level of p53–PEPD complex formation that was counteracted by hydrogen peroxide treatment. In this study, we found that silencing POX modulate pro-survival phenotype of MCF-7 cells and suggest that the mechanism of this process undergoes through down-regulation of p53-dependent signaling.
- Subjects
BREAST cancer; CELL death; PROLINE; CANCER cells; CELLULAR control mechanisms; APOPTOSIS; CASPASES
- Publication
Amino Acids, 2021, Vol 53, Issue 12, p1943
- ISSN
0939-4451
- Publication type
Article
- DOI
10.1007/s00726-021-03013-8