MassIVE MSV000094585

Complete Public PXD051617

Comparative label free proteomics analysis of MCF-7 and K562 cancer cells treated with mitomycin C and dicarbamoyl mitomycin C

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Description

Mitomycin C (MC) is an anti-cancer drug which functions by forming interstrand crosslinks between opposing DNA strands. MC analog, 10-decarbamoyl mitomycin C (DMC), unlike MC, has stronger cytotoxic effects on cancer with TP53 mutation. We previously demonstrated that MC/DMC could activate p21WAF1/CIP1 in MCF-7 (TP53-proficient) and K562 (TP53 mutant) cells in a TP53-independent mode. We also found that MC/DMC regulate Akt activation in a TP53-dependent manner and that the Akt deactivation is not associated with the activation of p21WAF1/CIP1 in response to MC/DMC treatment. RAS proteins are known players in the upstream mediated signaling of p21WAF1/CIP1 activation that leads to control of cell proliferation and cell death. Thus, this prompted us to investigate the effect of both drugs on the expression of RAS proteins and regulation of the MAPK/ERK signaling pathways in MCF-7 and K562 cancer cells. To accomplish this goal, we employed comparative label free proteomics profiling coupled to bioinformatics and complementary phosphoprotein arrays and western blot validations of key signaling molecules. The MAPK/ERK pathway exhibited an overall downregulation upon MC/DMC treatment in MCF-7 cells but only DMC exhibited a mild downregulation of that same pathway in TP53 mutant K562 cells. Furthermore, treatment of MCF-7 and K562 cell lines with oligonucleotides containing the interstrand crosslinks (ICLs) formed by MC or DMC shows that both ICLs had a stronger effect on the downregulation of RAS protein expression in mutant TP53 K562 cells. [doi:10.25345/C5TD9NK6W] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: bottom-up proteomics, mitomycin C and decarbamoyl mitomycin C treated MCF-7 and K-562 cancer cells

Contact

Principal Investigators:
(in alphabetical order) 		Cristina C Clement, Weill Cornell Medicine College, United States
Elise Champeil, John Jay College of Criminal Justice, the City University of New York (CUNY), United States
Submitting User: oriongalaxy
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