Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression.

Autor: Kurpińska A; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland., Suraj-Prażmowska J; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland., Stojak M; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland., Jarosz J; Hirszfeld Institute of Immunology and Experimental Therapy, Department of Experimental Oncology, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland., Mateuszuk Ł; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland., Niedzielska-Andres E; Faculty of Pharmacy, Chair and Department of Toxicology, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland., Smolik M; Faculty of Pharmacy, Chair and Department of Toxicology, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland., Wietrzyk J; Hirszfeld Institute of Immunology and Experimental Therapy, Department of Experimental Oncology, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland., Kalvins I; Laboratory of Carbofunctional Compounds, Latvian Institute of Organic Synthesis, Riga, 1006, Latvia. ivars.kalvins@lza.lv., Walczak M; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland. maria.walczak@jcet.eu.; Faculty of Pharmacy, Chair and Department of Toxicology, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland. maria.walczak@jcet.eu., Chłopicki S; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland. stefan.chlopicki@jcet.eu.; Faculty of Medicine, Chair of Pharmacology, Jagiellonian University Medical College, Grzegorzecka 16, 31-531, Krakow, Poland. stefan.chlopicki@jcet.eu.
Jazyk: angličtina
Zdroj: Cancer cell international [Cancer Cell Int] 2022 Jun 20; Vol. 22 (1), pp. 218. Date of Electronic Publication: 2022 Jun 20.
DOI: 10.1186/s12935-022-02631-w
Abstrakt: Background: Protein disulphide isomerases (PDIs) play an important role in cancer progression. However, the relative contribution of the various isoforms of PDI in tumorigenesis is not clear.
Methods: The content of PDI isoforms in 22 cancer cells lines was investigated using LC-MS/MS-based proteomic analysis. The effects of PDIA1, PDIA3 and PDIA17 inhibition on the proliferation, migration and adhesion of MCF-7 and MDA-MB-231 cells, identified as high and low PDIA17 expressing cells, respectively, were assessed using novel aromatic N-sulphonamides of aziridine-2-carboxylic acid derivatives as PDI inhibitors.
Results: PDIA1 and PDIA3 were the most abundant in cancer cell lysates and were also detected extracellularly in breast cancer cells (MDA-MB-231 and MCF-7). Some cancer cell lines (e.g., MCF-7, HT-29) showed upregulated expression of PDIA17, whereas in others (e.g., MDA-MB-231, 67NR), PDIA17 was not detected. The simultaneous inhibition of PDIA1 and PDIA3 showed similar anti-proliferative effects in MCF-7 and MDA-MB-231 breast cancer cells. However, the inhibition of PDIA1 and PDIA17 in the MCF-7 cell line resulted in more effective anti-adhesive and anti-proliferative effects.
Conclusions: PDIA1 and PDIA3 represent major isoforms of multiple cancer cells, and their non-selective inhibition displays significant anti-proliferative effects irrespective of whether or not PDIA17 is present. The more pronounced anti-adhesive effects of PDI inhibition in hormone-sensitive MCF-7 cells featured by higher levels of PDIs when compared to triple-negative MDA-MB-231 cells suggests that targeting extracellular PDIA1 and PDIA3 with or without additional PDIA17 inhibition may represent a strategy for personalized anti-adhesive, anti-metastatic therapy in cancers with high PDI expression.
(© 2022. The Author(s).)
Databáze: MEDLINE
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