Abstract

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 Limnothrix sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from Limnothrix 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 Limnothrix sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway.

Highlights

  • Phycobiliproteins (PBPs) are major components of the phycobilisome, the light-harvesting antenna for photosystem II in cyanobacteria and some red algae

  • We found that C-PC from Limnothrix sp

  • Bermejo-Bescós et al reported that protean extract and phycocyanin of Spirulina platensis increased antioxidant enzymatic activities and reactive oxygen species (ROS) scavenging in SH-SY5Y neuroblastoma cells and protected those cells against oxidative stress caused by iron radical scavenging ability [11]

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Summary

Introduction

Phycobiliproteins (PBPs) are major components of the phycobilisome, the light-harvesting antenna for photosystem II in cyanobacteria and some red algae. There is the increasing in potential of C-PCapplications that take advantage up to of all protein interest in cyanobacteria and pharmaceutical is used in manyuses commercial as a colorant in food or cosmetics, as a fluorescent and dye,anticancer and as a nutraceutical of itsnatural antioxidant, anti-inflammatory, hepatoprotective, effects [2,3].supplement in biomedical research [1]. Platinum-based chemotherapeutic agents, aminoglycoside antibiotics, loop diuretics, II) and carboplatin (cis-diammine 1,1-cyclobutane dicarboxylatoplatinum II) [5] are commonly used macrolide antibiotics, and antimalarials all have ototoxic effects [4]. ROS formation generation of excessive is considered to be one of thefollowing causative exposure pathogenesis of within the cochlea leads to aROS reduction in antioxidant enzymes to cisplatin cisplatin-induced ototoxicity [7]. KNUA002 has protective effects against cisplatin-induced ROS accumulation and ototoxicity in the mouse auditory cell line HEI-OC1

C-PC Alleviates Cisplatin-Induced Apoptosis in HEI-OC1 Cells
Effect of C-PC treatment ononcell cisplatin-treated
Effectby of flow
C-PC Effectively Reduces Intracellular ROS Levels in HEI-OC1 Cells
Materials and Methods
Cell Culture and Viability Assay
Cell Cycle Analysis
Detection of DNA Fragmentation
Measurement of Intracellular ROS Production
Protein Preparation
Western Blot Analysis
Conclusions
Full Text
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