Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • High doses of cisplatin more effectively suppress cancer, but high dose therapy is limited by nephrotoxic side effects, Nephrotoxicity is of critical concern during the early stages of drug development when selecting new drug candidates. Curcuma longa (CL) has been widely used for its anti-inflammatory, antioxidant and antitumour activities and has been taken orally to treat dyspepsia, flatulence and liver and urinary tract disease. WHAT THIS STUDY ADDS • New information indicated that the mechanism responsible for the effects of CL on HEK 293 cells was closely associated with regulation of the NFκB pathway. • This study confirmed the association of CL with the NFκB pathway. • CL may be an effective therapeutic approach to the alleviation of the progression of renal disease through cell anti-apoptosis and proliferation that occurs via inhibition of the inflammatory cytokines and the NFκB signaling pathway. AIM The rhizome of turmeric, Curcuma longa (CL), is a herbal medicine used in many traditional prescriptions. It has previously been shown that CL treatment showed greater than 47% recovery from cisplatin-induced cell damage in human kidney HEK 293 cells. This study was conducted to evaluate the recovery mechanisms of CL that occur during cisplatin induced nephrotoxicity by examining the genome wide mRNA expression profiles of HEK 293 -cells. METHOD Recovery mechanisms of CL that occur during cisplatin-induced nephrotoxicity were determined by microarray, real-time PCR, immunofluorescent confocal microscopy and Western blot analysis. RESULTS The results of microarray analysis and real-time PCR revealed that NFκB pathway-related genes and apoptosis-related genes were down-regulated in CL-treated HEK 293 cells. In addition, immunofluorescent confocal microscopy and Western blot analysis revealed that NFκB p65 nuclear translocation was inhibited in CL-treated HEK 293 cells. Therefore, the mechanism responsible for the effects of CL on HEK 293 cells is closely associated with regulation of the NFκB pathway. CONCLUSION CL possesses novel therapeutic agents that can be used for the prevention or treatment of cisplatin-induced renal disorders. © 2010 The British Pharmacological Society.

Author keywords

cisplatin; Curcuma longa; gene expression profile; HEK 293 cells

Indexed keywords

EMTREE drug terms: cisplatin; Curcuma longa extract; curcumin; immunoglobulin enhancer binding protein; messenger RNA; synaptotagmin I

EMTREE medical terms: apoptosis; article; cell proliferation; cell stimulation; cell strain HEK293; confocal microscopy; controlled study; Curcuma longa; down regulation; drug mechanism; gene expression profiling; genome; human; human cell; microarray analysis; nephrotoxicity; priority journal; real time polymerase chain reaction; Western blotting

MeSH: Antineoplastic Agents; Cell Line; Cisplatin; Curcuma; Down-Regulation; Gene Expression Profiling; Genome; Humans; Kidney Diseases; Microarray Analysis; NF-kappa B; Plant Extracts; Polymerase Chain Reaction
Medline is the source for the MeSH terms of this document.

Chemicals and CAS Registry Numbers: cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; curcumin, 458-37-7;Antineoplastic Agents; Cisplatin, 15663-27-1; NF-kappa B; Plant Extracts

Manufacturers:Drug manufacturer: Sun Ten, Taiwan.