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Rhodamine B-conjugated encrypted vipericidin nonapeptide is a potent toxin to zebrafish and associated with in vitro cytotoxicity
Liang Wang1; Judy Y.W. Chan1; Juciane V. Rêgo2,3; Cheong-Meng Chong1; Nana Ai1; Cláudio B. Falcão3; Gandhi Rádis-Baptista3; Simon M.Y. Lee1
2015
Source PublicationBiochimica et Biophysica Acta - General Subjects
ISSN18728006 03044165
Volume1850Issue:6Pages:1253-1260
Abstract

Abstract Background Animal venoms contain a diverse array of proteins and enzymes that are toxic toward various physiological systems. However, there are also some practical medicinal uses for these toxins including use as anti-bacterial and anti-tumor agents. Methods In this study, we identified a nine-residue cryptic oligopeptide, KRFKKFFKK (EVP50) that is repeatedly encoded in tandem within vipericidin sequences. Results EVP50 displayed in vivo potent lethal toxicity to zebrafish larvae (LD = 6 μM) when the peptide's N-terminus was chemically conjugated to rhodamine B (RhoB). In vitro, RhoB-conjugated EVP50 (RhoB-EVP50) exhibited a concentration-dependent cytotoxic effect toward MCF-7 and MDA-MB-231 breast cancer cells. In MCF-7 cells, the RhoB-EVP50 nonapeptide accumulated inside the cells within minutes. In the cytoplasm, the RhoB-EVP50 induced extracellular calcium influx and intracellular calcium release. Membrane budding was also observed after incubation with micromolar concentrations of the fluorescent EVP50 conjugate. Conclusions The conjugate's interference with calcium homeostasis, its intracellular accumulation and its induced membrane dysfunction (budding and vacuolization) seem to act in concert to disrupt the cell circuitry. Contrastively, unconjugated EVP50 peptide did not display neither toxic nor cytotoxic activities in our in vivo and in vitro models. General significance The synergic mechanism of toxicity was restricted to the structurally modified encrypted vipericidin nonapeptide.

KeywordCell-penetrating Peptide Cytotoxin Encrypted Peptides Rhodamine B-conjugated Peptide Vipericidins Zebra-fish Model
DOI10.1016/j.bbagen.2015.02.013
URLView the original
Indexed BySCIE
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics
WOS SubjectBiochemistry & Molecular Biology ; Biophysics
WOS IDWOS:000353736100017
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorGandhi Rádis-Baptista; Simon M.Y. Lee
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Northeast Biotechnology Network (RENORBIO), Post-graduation program in Biotechnology, Federal University of Ceara, Brazil
3.Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceara, Brazil
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Liang Wang,Judy Y.W. Chan,Juciane V. Rêgo,et al. Rhodamine B-conjugated encrypted vipericidin nonapeptide is a potent toxin to zebrafish and associated with in vitro cytotoxicity[J]. Biochimica et Biophysica Acta - General Subjects,2015,1850(6):1253-1260.
APA Liang Wang.,Judy Y.W. Chan.,Juciane V. Rêgo.,Cheong-Meng Chong.,Nana Ai.,...&Simon M.Y. Lee.(2015).Rhodamine B-conjugated encrypted vipericidin nonapeptide is a potent toxin to zebrafish and associated with in vitro cytotoxicity.Biochimica et Biophysica Acta - General Subjects,1850(6),1253-1260.
MLA Liang Wang,et al."Rhodamine B-conjugated encrypted vipericidin nonapeptide is a potent toxin to zebrafish and associated with in vitro cytotoxicity".Biochimica et Biophysica Acta - General Subjects 1850.6(2015):1253-1260.
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