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Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin
- Source :
- International Journal of Oncology. 38
- Publication Year :
- 2011
- Publisher :
- Spandidos Publications, 2011.
-
Abstract
- Flavin adenine dinucleotide (FAD) is an essential coenzyme for glutathione reductase (GR) which catalyzes the reduction of oxidized glutathione to regenerate the reduced form involved in protection against oxidative stress. Riboflavin kinase (RFK) also known as flavokinase is involved in the first step of bioactivation of riboflavin (RF) to form flavin mononucleotide (FMN) which can be subsequently converted to FAD in an ATP-dependent reaction catalyzed by FAD synthetase (FADS). We investigated the involvement of RFK in cisplatin resistance using human prostate cancer PC3 cells. RFK overexpression renders cells resistant not only to cisplatin but also to hydrogen peroxide (H2O2) and diamide. Furthermore, knockdown of RFK expression induced apoptosis. We demonstrated that overexpression of RFK increased the levels of FAD, FMN and total glutathione and the expression of GR and glutathione S-transferase-π (GSTπ). RFK expression is up-regulated in cisplatin-resistant P/CDP6 cells in addition to FAD, total glutathione level, GR and GSTπ. Knockdown of RFK expression also sensitized both PC3 and P/CDP6 cells to cisplatin. Moreover, cellular levels of RFK expression correlate well with Gleason score, known as a good indicator of patient prognosis. The present study suggests that RFK expression is involved not only in cellular protection from oxidative stress but also in malignant progression of prostate cancer.
- Subjects :
- Male
Cancer Research
Cell Survival
Glutathione reductase
Flavin mononucleotide
Antineoplastic Agents
Flavin group
Biology
Riboflavin kinase
Cofactor
chemistry.chemical_compound
Cell Line, Tumor
Flavins
Humans
heterocyclic compounds
Cell Proliferation
Etoposide
Diamide
Flavin adenine dinucleotide
FAD synthetase
Prostatic Neoplasms
Hydrogen Peroxide
Glutathione
Oxidants
Recombinant Proteins
Oxidative Stress
Phosphotransferases (Alcohol Group Acceptor)
Oncology
chemistry
Biochemistry
Drug Resistance, Neoplasm
biology.protein
Cisplatin
Subjects
Details
- ISSN :
- 10196439
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- International Journal of Oncology
- Accession number :
- edsair.doi.dedup.....743a29d9c4543eeddcbe6c44a4e451db