The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.
Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits. In earlier work we identified and characterize Protein DJ-1 (PARK7) as an oxidative stress squevenger in renal cells exposed to oxidative stress. To investigate whether the PARK7 or other oxidative stress proteins play a role in the renal cell carcinoma and its sensitivity or resistance to cytostatic drug treatment, differential proteomics analysis was performed with a cell model for clear cell renal carcinoma (Caki-2 and A498). Caki-2 cells were treated with cisplatin and differentially expressed proteins were investigated. The cisplatin treatment resulted in an increase in reactive oxygen species accumulation and ultimately apoptosis of Caki-2 and A498 cells. In parallel, the apoptotic effect was accompanied by a significant downregulation of antioxidant proteins especially PARK7. Knockdown of PARK7 using siRNA and overexpression using plasmid highlights the role of PARK7 as a key player in renal cell carcinoma response to cisplatin induced apoptosis. Overexpression of PARK7 resulted in significant decrease in apoptosis, whereas knockdown of the protein was accompanied by an increase in apoptosis in Caki-2 and A498 cells treated with cisplatin. These results highlights for the first time the important role of PARK7 in cisplatin induced apoptosis in clear renal cell carcinoma cells.
Clinic for Nephrology and Rheumatology, University Medical Centre, Georg-August University Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany; Cell Death Research Laboratory, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Rachana
R
Trivedi
Clinic for Nephrology and Rheumatology, University Medical Centre, Georg-August University Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany.
Gry H
GH
Dihazi
Clinic for Nephrology and Rheumatology, University Medical Centre, Georg-August University Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany.
Marwa
M
Eltoweissy
Cell Death Research Laboratory, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Durga P
DP
Mishra
Clinic for Nephrology and Rheumatology, University Medical Centre, Georg-August University Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany.
Gerhard A
GA
Mueller
Clinic for Nephrology and Rheumatology, University Medical Centre, Georg-August University Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany. Electronic address: dihazi@med.uni-goettingen.de.
Hassan
H
Dihazi
D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019295:Computational Biology; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D000071617:Protein Deglycase DJ-1 / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D020543:Proteome; D017382:Reactive Oxygen Species; D000071617:Protein Deglycase DJ-1; D002945:Cisplatin
6-diamidino-2-phenylindole (PubChem CID: 160166); Apoptosis; CHAPS (PubChem CID: 107670); Caki-2; Cisplatin; Cisplatin (PubChem CID: 441203); DTT (PubChem CID: 446094); H2DCFDA (PubChem CID: 77718); PARK7; PMSF (PubChem CID: 4784); Reactive oxygen species; Renal cell carcinoma; Tris (PubChem CID: 93573); acetonitrile (PubChem CID: 6342); bromophenol blue (PubChem CID: 8272); glycerol (PubChem CID: 753); iodoacetamide (PubChem CID: 3727); l-glutamine (PubChem CID: 5961); paraformaldehyde solution (PubChem CID: 712); penicillin (PubChem CID: 5904); propidium iodide (PubChem CID: 104981); streptomycin (PubChem CID: 19649); trifluoroacetic acid (PubChem CID: 6422); urea (PubChem CID: 1176)