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A novel microtubule de-stabilizing complementarity-determining region C36L1 peptide displays antitumor activity against melanoma in vitro and in vivo

Figueiredo CR; Azevedo RA; Girola N; Massaoka MH; Matsuo AL; Polonelli L; Travassos LR

dc.contributor.authorFigueiredo CR
dc.contributor.authorAzevedo RA
dc.contributor.authorGirola N
dc.contributor.authorMassaoka MH
dc.contributor.authorMatsuo AL
dc.contributor.authorPolonelli L
dc.contributor.authorTravassos LR
dc.date.accessioned2022-10-28T14:42:24Z
dc.date.available2022-10-28T14:42:24Z
dc.identifier.urihttps://www.utupub.fi/handle/10024/172888
dc.description.abstractShort peptide sequences from complementarity-determining regions (CDRs) of different immunoglobulins may exert anti-infective, immunomodulatory and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). In this sense, they resemble early molecules of innate immunity. C36L1 was identified as a bioactive light-chain CDR1 peptide by screening 19 conserved CDR sequences targeting murine B16F10-Nex2 melanoma. The 17-amino acid peptide is readily taken up by melanoma cells and acts on microtubules causing depolymerization, stress of the endoplasmic reticulum and intrinsic apoptosis. At low concentrations, C36L1 inhibited migration, invasion and proliferation of B16F10-Nex2 cells with cell cycle arrest at G2/M phase, by regulating the PI3K/Akt signaling axis involving Rho-GTPase and PTEN mediation. Peritumor injection of the peptide delayed growth of subcutaneously grafted melanoma cells. Intraperitoneal administration of C36L1 induced a significant immune-response dependent anti-tumor protection in a syngeneic metastatic melanoma model. Dendritic cells stimulated ex-vivo by the peptide and transferred to animals challenged with tumor cells were equally effective. The C36 VL CDR1 peptide is a promising microtubule-interacting drug that induces tumor cell death by apoptosis and inhibits metastases of highly aggressive melanoma cells.
dc.titleA novel microtubule de-stabilizing complementarity-determining region C36L1 peptide displays antitumor activity against melanoma in vitro and in vivo
dc.identifier.urlhttps://www.nature.com/articles/srep14310
dc.identifier.urnURN:NBN:fi-fe2021042827645
dc.relation.volume5
dc.contributor.organizationfi=MediCity|en=MediCity Research Laboratory|
dc.contributor.organization-code2607003
dc.converis.publication-id41090960
dc.converis.urlhttps://research.utu.fi/converis/portal/Publication/41090960
dc.identifier.eissn2045-2322
dc.identifier.jour-issn2045-2322
dc.okm.affiliatedauthorDe Figueiredo, Rogerio
dc.okm.discipline1182 Biochemistry, cell and molecular biologyen_GB
dc.okm.discipline1182 Biokemia, solu- ja molekyylibiologiafi_FI
dc.okm.internationalcopublicationinternational co-publication
dc.okm.internationalityInternational publication
dc.okm.typeJournal article
dc.relation.doi10.1038/srep14310
dc.relation.ispartofjournalScientific Reports
dc.year.issued2015


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