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

Abstract

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 (10μg/mL) significantly reduced neurite outgrowth. The tested concentration of curcumin (1.0 and 10μg/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.

Curcumin alleviates cisplatin-induced learning and memory impairments

“…Therefore, it cannot readily pass the blood-brain barrier (BBB) under normal physiological conditions. As a result, previous researchers are mainly focused on cisplatin-induced neurotoxicity in the peripheral nervous system (Erken et al, 2014;Tuncer et al, 2010) and neural cell culture environment Mendonca et al, 2013). However, cisplatin has been detected that can penetrate the BBB under altered physiological conditions such as short-term hypoxia (Minami et al, 1996).…”

“…Oxidative stress may be the most important mechanism among these mechanisms that are proposed to explain neurotoxicity, and in this regard, targeting oxidative stress can limit cisplatininduced neurotoxicity while preserving anticancer efficacy. Therefore, several antioxidant molecules such as coenzyme Q10 (da Silva , walnut (Shabani et al, 2012b), D-Methionine (Gopal et al, 2012), alpha lipoic acid (Tuncer et al, 2010), melatonin (Tuncer et al, 2010), and curcumin (Al Moundhri et al, 2013;Mendonca et al, 2013) have been used to in an effort to either mitigate or prevent cisplatin-induced neurotoxicity.…”

The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update

“…In addition, curcumin is reported to decrease cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells (Mendonca et al, 2013), increase phosphorylation of ERK1/2 and induced protein expression of tumour suppressor p53 and FOXO3a in a dose-dependent manner in nasopharyngeal carcinoma . This resulted in metastasis inhibition (Roy et al, 2013).…”

Curcumin: an adjuvant therapeutic remedy for liver cancer

“…Mendonca et al [68] reported the neuroprotective effect of curcumin against cisplatin induced cytotoxicity without any interference of curcumin with the cytotoxic activity of cisplatin.…”