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conferenceseries.com
Volume 9, Issue 9 (Suppl) J Cancer Sci Ther, an open access journal
ISSN: 1948-5956 World Cancer 2017
October 19-21, 2017
25th WORLD CANCER CONFERENCE
October 19-21, 2017 | Rome, Italy
HuAL1 peptide from complementarity-determining region 1 (CDR-1) of mAb HuA induces necroptosis in
B16F10-Nex2 cells
Denise C Arruda1, Felipe V Pereira2, Luana C P Santos2, Filipe M Melo3, Aline N Rabaça3, Elaine G Rodrigues3, Renato A Mortara3, Luciano Polonelli4
and Luiz R Travassos3
1Universidades de Mogi das Cruzes, Brazil
2University of São Paulo, Brazil
3Federal University of São Paulo, Brazil
4University of Parma, Italy
Treatment of melanoma, mainly on the metastatic stage, is a great clinical challenge because conventional chemotherapy
is rather ineffective. Other strategies, including immunotherapy, have been introduced and are very encouraging. We
have previously shown that peptides derived from complementarity determining regions of immunoglobulins (CDRs) display
antimicrobial and antitumor activities regardless of the specificity of the antibodies they were derived from. In the present
study, we show that CDR 1 from the light chain (L1) of a human IgM, mAb (HuA), specific for difucosyl human blood
group A (HuA) induces necroptotic cell death in the murine melanoma cell line B16F10-Nex2 and in other murine and
human tumor cell lines. HuAL1 did not exert cytotoxic effects in non-tumorigenic cell lines. Melanoma cells treated with
HuAL1 showed DNA degradation, propidium iodide incorporation and abundant superoxide anion production. Moreover,
peptide treatment induced mitochondrial swelling and disruption of mitochondrial cristae. All these effects were caspase-
independent and RIPK1- and MLKL-dependent, since cell death was abolished when cells were co-incubated with necrostatin
or necrosulfonamide. Confocal microscopy showed that HuAL1 peptide localizes to the cell nucleus, and ELISA assay showed
that it probably binds to H3 histone. We propose that necroptosis is induced after chromatin disorganization upon peptide
binding to histone. Our results show, for the first time, that a peptide derived from an Ig-CDR can induce necroptotic cell death
on tumor cells.
Biography
Denise C Arruda is graduated in Pharmacy from the Federal University of Santa Catarina in 2000. She pursued PhD in Biology Sciences from University of
São Paulo (ICB-USP) with postdoctoral degree at the Experimental Oncology Unit - Discipline of Cell Biology, Federal University of São Paulo from 2008-2014.
Currently, she is a professor and researcher at the Integrated Nucleus of Biotechnology at University of Mogi das Cruzes. She has published 17 papers in reputed
journals, some of them in collaboration with international research groups, and received awards for poster presentation in five international meetings.
Denise C Arruda et al., J Cancer Sci Ther 2017, 9:9(Suppl)
DOI: 10.4172/1948-5956-C1-112