C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells

Ototoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no e...

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Main Authors: Ye-Ri Kim, Jeong-Mi Do, Kyung Hee Kim, Alexandra R. Stoica, Seung-Woo Jo, Un-Kyung Kim, Ho-Sung Yoon
Format: Article
Language:English
Published: MDPI AG 2019-04-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/17/4/235
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author Ye-Ri Kim
Jeong-Mi Do
Kyung Hee Kim
Alexandra R. Stoica
Seung-Woo Jo
Un-Kyung Kim
Ho-Sung Yoon
author_facet Ye-Ri Kim
Jeong-Mi Do
Kyung Hee Kim
Alexandra R. Stoica
Seung-Woo Jo
Un-Kyung Kim
Ho-Sung Yoon
author_sort Ye-Ri Kim
collection DOAJ
description Ototoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no effective treatment for it. The generation of excessive reactive oxygen species (ROS) is considered to be the major cause of cisplatin-induced ototoxicity. C-phycocyanin (C-PC), a blue phycobiliprotein found in cyanobacteria and red algae, has antioxidant and anticancer activities in different experimental models in vitro and in vivo. Thus, we tested the ability of C-PC from <i>Limnothrix</i> sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from <i>Limnothrix</i> sp. KNUA002 inhibited apoptosis and protected mitochondrial function by preventing ROS accumulation in cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, a mouse auditory cell line. Cisplatin increased the expression of Bax and reduced the expression of Bcl-2, which activate and inhibit, respectively, the mitochondrial apoptotic pathway in response to oxidative stress. Pretreatment with C-PC prior to cisplatin treatment caused the Bax and Bcl-2 levels to stay close to the levels in untreated control cells. Our results suggest that C-PC from <i>Limnothrix</i> sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway.
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spelling doaj.art-57a16cab74b846b8992412567f5c79a92022-12-22T04:09:38ZengMDPI AGMarine Drugs1660-33972019-04-0117423510.3390/md17040235md17040235C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory CellsYe-Ri Kim0Jeong-Mi Do1Kyung Hee Kim2Alexandra R. Stoica3Seung-Woo Jo4Un-Kyung Kim5Ho-Sung Yoon6Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaOtotoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no effective treatment for it. The generation of excessive reactive oxygen species (ROS) is considered to be the major cause of cisplatin-induced ototoxicity. C-phycocyanin (C-PC), a blue phycobiliprotein found in cyanobacteria and red algae, has antioxidant and anticancer activities in different experimental models in vitro and in vivo. Thus, we tested the ability of C-PC from <i>Limnothrix</i> sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from <i>Limnothrix</i> sp. KNUA002 inhibited apoptosis and protected mitochondrial function by preventing ROS accumulation in cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, a mouse auditory cell line. Cisplatin increased the expression of Bax and reduced the expression of Bcl-2, which activate and inhibit, respectively, the mitochondrial apoptotic pathway in response to oxidative stress. Pretreatment with C-PC prior to cisplatin treatment caused the Bax and Bcl-2 levels to stay close to the levels in untreated control cells. Our results suggest that C-PC from <i>Limnothrix</i> sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway.https://www.mdpi.com/1660-3397/17/4/235ototoxicitycisplatinC-phycocyanin<i>Limnothrix</i>HEI-OC1
spellingShingle Ye-Ri Kim
Jeong-Mi Do
Kyung Hee Kim
Alexandra R. Stoica
Seung-Woo Jo
Un-Kyung Kim
Ho-Sung Yoon
C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells
Marine Drugs
ototoxicity
cisplatin
C-phycocyanin
<i>Limnothrix</i>
HEI-OC1
title C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells
title_full C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells
title_fullStr C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells
title_full_unstemmed C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells
title_short C-phycocyanin from <i>Limnothrix</i> Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells
title_sort c phycocyanin from i limnothrix i species knua002 alleviates cisplatin induced ototoxicity by blocking the mitochondrial apoptotic pathway in auditory cells
topic ototoxicity
cisplatin
C-phycocyanin
<i>Limnothrix</i>
HEI-OC1
url https://www.mdpi.com/1660-3397/17/4/235
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