4.4 Article

Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells

期刊

NEUROTOXICOLOGY
卷 34, 期 -, 页码 205-211

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.neuro.2012.09.011

关键词

Chemoprotection; Neurite outgrowth assay; p53; Gene expression; Cytotoxicity

资金

  1. CAPES (Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior)
  2. CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
  3. FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2008/53947-7]
  4. FAPESP [2008/10482-4]

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The potential neuroprotective benefits of curcumin against cisplatin neurotoxicity were investigated. Curcumin is a polyphenol derived from the rhizome of Curcuma longa whose pharmacological effects include antioxidant, anti-inflammatory and anti-cancer properties. Cisplatin is a potent chemotherapeutic drug with activity against a wide variety of tumors, although it has notorious side effects. Cisplatin neurotoxicity is clinically evident in patients that have undergone a full course of chemotherapy and develop a peripheral neuropathy that may affect the treatment regimen and the patient's qualify of life. In this study, we examined whether curcumin can protect against cisplatin neurite outgrowth inhibition in PC12 cells, which is an indicator of the protective potential against neuropathy. We also investigated whether curcumin affects cisplatin effectiveness by analyzing the modulation of p53 gene expression and its effect on cisplatin cytotoxicity in HepG2 tumor cells. Non-cytotoxic concentrations of curcumin reduced in vitro neurotoxicity of cisplatin in PC12 cells. The treatment of PC12 cells with cisplatin (10 mu g/mL) significantly reduced neurite outgrowth. The tested concentration of curcumin (1.0 and 10 mu g/mL) did not result in neurite toxicity but nevertheless diminished cisplatin-induced inhibition of neurite outgrowth by up to 50% (p < 0.05). Our results indicate that curcumin does not compromise cisplatin's anticancer activity. Curcumin neither suppressed p53 mRNA transcription nor protected tumor cells against cisplatin cytotoxicity. These results indicate that curcumin may reduce cisplatin-induced neurotoxicity, and clinical studies should potentially be considered. (C) 2012 Elsevier Inc. All rights reserved.

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