Universität zu Köln

Moeltgen, Sophie, Piumatti, Eleonora, Massafra, Giuseppe M., Metzger, Sabine, Jaehde, Ulrich and Kalayda, Ganna, V (2020). Cisplatin Protein Binding Partners and Their Relevance for Platinum Drug Sensitivity. Cells, 9 (6). BASEL: MDPI. ISSN 2073-4409

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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 pi, 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 pi 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Moeltgen, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Piumatti, Eleonora UNSPECIFIED UNSPECIFIED UNSPECIFIED Massafra, Giuseppe M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaehde, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalayda, Ganna, V UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-331147
DOI:	10.3390/cells9061322
Journal or Publication Title:	Cells
Volume:	9
Number:	6
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language 2-DIMENSIONAL GEL-ELECTROPHORESIS; S-TRANSFERASE-PI; OVARIAN-CANCER; GLUTATHIONE TRANSFERASES; RESISTANCE; OXALIPLATIN; VIMENTIN; CELLS; COMBINATION; COMPLEXES Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33114