Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats

• Published in: Integrative cancer therapies 2019-08, Vol.18, p.1534735419872811-1534735419872811
• Main Authors: Dhima, Irida, Zerikiotis, Stelios, Lekkas, Panagiotis, Simos, Yannis V., Gkiouli, Maria, Vezyraki, Patra, Dounousi, Evangelia, Ragos, Vasilios, Giannakopoulos, Xenophon, Baltogiannis, Dimitrios, Kalfakakou, Vasiliki, Evangelou, Angelos, Peschos, Dimitrios, Karkabounas, Spyridon
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antioxidants; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; Blood; Blood Urea Nitrogen; Cell cycle; Cell Line; Cell proliferation; Cell viability; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Creatinine; Creatinine - metabolism; Curcumin; Curcumin - pharmacology; Enzymatic activity; Enzymes; Female; Free radicals; Glutathione - metabolism; Glutathione peroxidase; Humans; Kidney - drug effects; Kidney - metabolism; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; Kidneys; Leiomyosarcoma - drug therapy; Leiomyosarcoma - metabolism; Lipid peroxidation; Lipid Peroxidation - drug effects; Malondialdehyde; Mitochondria; Nephrons; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Wistar; Side effects; Superoxide dismutase; Superoxide Dismutase - metabolism; Urea; Urine
• ISSN: 1534-7354; 1552-695X
• DOI: 10.1177/1534735419872811

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney’s relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats’ blood and malondialdehyde levels in rats’ urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood’s antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons’ histology from cisplatin’s toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.