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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Effects of Alpha-Connexin Carboxyl-Terminal Peptide (aCT1) and Bowman-Birk Protease Inhibitor (BBI) on Canine Oral Mucosal Melanoma (OMM) Cells

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Author(s):
Sato, Ayami [1, 2] ; da Fonseca, Ivone Izabel Mackowiak [1] ; Nagamine, Marcia Kazumi [1] ; de Toledo, Gabriela Fernandes [1] ; Olio, Rennan [1] ; Hernandez-Blazquez, Francisco Javier [1] ; Yano, Tomohiro [2] ; Yeh, Elizabeth Shinmay [3] ; Dagli, Maria Lucia Zaidan [1]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Sch Vet Med & Anim Sci, Sao Paulo - Brazil
[2] Toyo Univ, Inst Life Innovat Studies, Tokyo - Japan
[3] Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Simon Comprehens Canc Ctr, Indianapolis, IN 46202 - USA
Total Affiliations: 3
Document type: Journal article
Source: FRONTIERS IN VETERINARY SCIENCE; v. 8, JUN 10 2021.
Web of Science Citations: 0
Abstract

Oral mucosal melanomas (OMM) are aggressive cancers in dogs, and are good models for human OMM. Gap junctions are composed of connexin units, which may have altered expression patterns and/or subcellular localization in cancer cells. Cell-to-cell communication by gap junctions is often impaired in cancer cells, including in melanomas. Meanwhile, the upregulated expression of the gap junction protein connexin 43 (Cx43) inhibits melanoma progression. The alpha-connexin carboxyl-terminal (aCT1) peptide reportedly maintains Cx43 expression and cell-cell communication in human mammary cells and increases the communication activity through gap junctions in functional assays, therefore causing decreased cell proliferation. The Bowman-Birk protease inhibitor (BBI), a component of soybeans, induces Cx43 expression in several tumor cells as a trypsin-chymotrypsin inhibition function, with antineoplastic effects. This study investigated the effect of aCT1 peptide and BBI treatment, alone or in combination, on TLM1 canine melanoma cell viability. Cell viability after treatment with aCT1, the reverse sequence peptide (R-pep), and/or BBI for 5 days was analyzed by PrestoBlue assay. Immunofluorescence was used to observe Cx43 localization and expression. aCT1 (200 mu M) alone did not significantly decrease cell viability in TLM1 cells, whereas BBI (400 mu g/ml) alone significantly decreased the TLM1 viability. Combined treatment with both aCT1 (200 mu M) and BBI (400 mu g/ml) significantly decreased cell viability in TLM1 cells. Cx43 expression, as identified by immunostainings in TLM1 cells, was increased in the cell membrane after the combination treatment with BBI and aCT1. This dual treatment can be combined to achieve the anticancer activity, possibly by increasing Cx 43 expression and affecting Cx43 migration to the cell membrane. In conclusion, a treatment strategy targeting Cx43 with BBI and aCT1 may possibly lead to new effective therapies for canine OMM. (AU)

FAPESP's process: 16/20479-7 - Evaluation of the effects of urokinase-activated (uPA) and metalloproteinases (MMPs) toxin on Canine Hemangiosarcoma: in vitro and in vivo studies
Grantee:Márcia Kazumi Nagamine
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/11202-7 - Effects of treatment with ACT1 treatment on cell proliferation of B16 melanoma and canine melanoma cells.
Grantee:Ayami Sato
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 17/12855-1 - Investigation of the carboxyl-terminal Q-connexin peptide (ACT1) activity associated with the inhibitor of histone deacetylases sodium butyrate, and conventional chemotherapeutic agents, on the treatment of canine mammary tumors: in vitro assays.
Grantee:Ivone Izabel Mackowiak da Fonseca
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/16515-3 - Antineoplastic effects of Dichloroacetate sodium (DCA) and omeprazole (OMP) in canine oral malignant melanoma cell lines: a study of the mechanisms of action
Grantee:Gabriela Fernandes de Toledo
Support Opportunities: Scholarships in Brazil - Master