Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats
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 radica...
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doaj-a0e7d18471bf402898b17ed9b5a615442020-11-25T03:24:01ZengSAGE PublishingIntegrative Cancer Therapies1552-695X2019-08-011810.1177/1534735419872811Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in RatsIrida Dhima MSc, PhD0Stelios Zerikiotis MSc, PhD1Panagiotis Lekkas MSc, PhD2Yannis V. Simos MSc (MedSci), PhD3Maria Gkiouli MSc, PhD4Patra Vezyraki MD, PhD5Evangelia Dounousi MD, PhD6Vasilios Ragos MD, PhD7Xenophon Giannakopoulos MD, PhD8Dimitrios Baltogiannis MD, PhD9Vasiliki Kalfakakou MD, PhD10Angelos Evangelou MD, PhD11Dimitrios Peschos MD, PhD12Spyridon Karkabounas PhD13University of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceUniversity of Ioannina, GreeceBackground. 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.https://doi.org/10.1177/1534735419872811 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Irida Dhima MSc, PhD Stelios Zerikiotis MSc, PhD Panagiotis Lekkas MSc, PhD Yannis V. Simos MSc (MedSci), PhD Maria Gkiouli MSc, PhD Patra Vezyraki MD, PhD Evangelia Dounousi MD, PhD Vasilios Ragos MD, PhD Xenophon Giannakopoulos MD, PhD Dimitrios Baltogiannis MD, PhD Vasiliki Kalfakakou MD, PhD Angelos Evangelou MD, PhD Dimitrios Peschos MD, PhD Spyridon Karkabounas PhD |
spellingShingle |
Irida Dhima MSc, PhD Stelios Zerikiotis MSc, PhD Panagiotis Lekkas MSc, PhD Yannis V. Simos MSc (MedSci), PhD Maria Gkiouli MSc, PhD Patra Vezyraki MD, PhD Evangelia Dounousi MD, PhD Vasilios Ragos MD, PhD Xenophon Giannakopoulos MD, PhD Dimitrios Baltogiannis MD, PhD Vasiliki Kalfakakou MD, PhD Angelos Evangelou MD, PhD Dimitrios Peschos MD, PhD Spyridon Karkabounas PhD Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats Integrative Cancer Therapies |
author_facet |
Irida Dhima MSc, PhD Stelios Zerikiotis MSc, PhD Panagiotis Lekkas MSc, PhD Yannis V. Simos MSc (MedSci), PhD Maria Gkiouli MSc, PhD Patra Vezyraki MD, PhD Evangelia Dounousi MD, PhD Vasilios Ragos MD, PhD Xenophon Giannakopoulos MD, PhD Dimitrios Baltogiannis MD, PhD Vasiliki Kalfakakou MD, PhD Angelos Evangelou MD, PhD Dimitrios Peschos MD, PhD Spyridon Karkabounas PhD |
author_sort |
Irida Dhima MSc, PhD |
title |
Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats |
title_short |
Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats |
title_full |
Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats |
title_fullStr |
Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats |
title_full_unstemmed |
Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats |
title_sort |
curcumin acts as a chemosensitizer for leiomyosarcoma cells in vitro but fails to mediate antioxidant enzyme activity in cisplatin-induced experimental nephrotoxicity in rats |
publisher |
SAGE Publishing |
series |
Integrative Cancer Therapies |
issn |
1552-695X |
publishDate |
2019-08-01 |
description |
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. |
url |
https://doi.org/10.1177/1534735419872811 |
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