Cisplatin Protein Binding Partners and Their Relevance for Platinum Drug Sensitivity.
Sophie Möltgen,Eleonora Piumatti,Giuseppe M Massafra,Sabine Metzger,Sabine Metzger,Ulrich Jaehde,Ganna V. Kalayda,Ganna V. Kalayda +7 more
TLDR
The silencing of glutathione-S-transferase π significantly sensitized intrinsically resistant HCT-8 and H CT-8ox cells to cisplatin, suggesting a possible involvement of the protein in the resistance of colorectal cancer cells to the drug.Abstract:
Cisplatin is a widely used drug in the treatment of various solid tumors, such as ovarian cancer. However, while the acquired resistance significantly limits the success of therapy, some tumors, such as colorectal cancer, are intrinsically insensitive to cisplatin. Only a small amount of intracellular platinum binds to the target—genomic DNA. The fate of the remaining drug is largely obscure. This work aimed to identify the cytosolic protein binding partners of cisplatin in ovarian and colorectal cancer cells and to evaluate their relevance for cell sensitivity to cisplatin and oxaliplatin. Using the fluorescent cisplatin analog BODIPY-cisplatin, two-dimensional gel electrophoresis, and mass spectrometry, we identified the protein binding partners in A2780 and cisplatin-resistant A2780cis ovarian carcinoma, as well as in HCT-8 and oxaliplatin-resistant HCT-8ox colorectal cell lines. Vimentin, only identified in ovarian cancer cells; growth factor receptor-bound protein 2, only identified in colorectal cancer cells; and glutathione-S-transferase π, identified in all four cell lines, were further investigated. The effect of pharmacological inhibition and siRNA-mediated knockdown on cytotoxicity was studied to assess the relevance of these binding partners. The silencing of glutathione-S-transferase π significantly sensitized intrinsically resistant HCT-8 and HCT-8ox cells to cisplatin, suggesting a possible involvement of the protein in the resistance of colorectal cancer cells to the drug. The inhibition of vimentin with FiVe1 resulted in a significant sensitization of A2780 and A2780cis cells to cisplatin, revealing new possibilities for improving the chemosensitivity of ovarian cancer cells.read more
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Cisplatin-mediated activation of glucocorticoid receptor induces platinum resistance via MAST1
Chaoyun Pan,JiHoon Kang,Jung Seok Hwang,Jie Li,Austin C. Boese,Xu Wang,Li-Kun Yang,Titus J. Boggon,Georgia Z. Chen,Nabil F. Saba,Dong M. Shin,Kelly R. Magliocca,Lingtao Jin,Sumin Kang +13 more
TL;DR: In this paper, the authors show that glucocorticoid receptor (GR) upregulated upon cisplatin exposure through activated transcription factor GR and MAST1 upregulation coordinately occur in patient tumors collected after platinum treatment, and align with patient treatment resistance.
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Redox modulation of vitagenes via plant polyphenols and vitamin D: Novel insights for chemoprevention and therapeutic interventions based on organoid technology.
Maria Scuto,Angela Trovato Salinaro,Isabella Caligiuri,Maria Laura Ontario,Valentina Greco,Nello Sciuto,Roberto Crea,Edward J. Calabrese,Flavio Rizzolio,Vincenzo Canzonieri,Vittorio Calabrese +10 more
TL;DR: In this paper, the importance of vitagenes in redox stress response and autophagy mechanisms, as well as the potential use of dietary antioxidants in the prevention and treatment of multiple types of cancer are discussed.
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Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position.
Daniil Spector,K. G. Pavlov,Roman Akasov,Alexander Vaneev,Alexander Erofeev,Petr V. Gorelkin,Vita N. Nikitina,Elena V Lopatukhina,A. S. Semkina,Kseniya Yu. Vlasova,Dmitrii A. Skvortsov,Vitaly A. Roznyatovsky,Nikolay Ul'yanovskiy,I. I. Pikovskoi,S. A. Sypalov,Anastasiia S Garanina,Stepan Vodopyanov,Maxim A. Abakumov,Yulia L. Volodina,Alina A. Markova,Albina S. Petrova,D. M. Mazur,D. A. Sakharov,Nikolai V. Zyk,Elena K. Beloglazkina,Alexander G. Majouga,Olga O. Krasnovskaya +26 more
TL;DR: The design, synthesis, and biological investigation of a series of novel Pt(IV) prodrugs with non-steroidal anti-inflammatory drugs naproxen, diclofenac, and flurbiprofen, as well as these with stearic acid in the axial position showing superior antiproliferative activity compared to cisplatin are reported.
Journal ArticleDOI
PD-1/PD-L1 and DNA Damage Response in Cancer
Mateusz Kciuk,Damian Kołat,Żaneta Kałuzińska-Kołat,Mateusz Gawrysiak,Rafał Drozda,Ismail Celik,Renata Kontek +6 more
TL;DR: In this paper , the effect of etoposide, irinotecan, and platinum compounds on the PD-L1 expression of cancer cells has been studied and compared.
Journal ArticleDOI
Critical factors affecting the albumin binding of half-sandwich Ru(II) and Rh(III) complexes of 8-hydroxyquinolines and oligopyridines
Orsolya Dömötör,Tamás Pivarcsik,János P. Mészáros,Istvan Szatmari,Ferenc Fülöp,Éva A. Enyedy +5 more
TL;DR: In this article, the interaction of half-sandwich anticancer organometallic complexes with proteins was studied in detail by means of various methods such as 1H NMR spectroscopy, UV-visible spectrophotometry, steady-state and time-resolved fluorometry, ultrafiltration and capillary zone electrophoresis.
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