Inhibition of Breast Cancer Cell Migration by Cyclotides Isolated from Pombalia calceolaria.

Autor: Pinto MEF; Institute of Chemistry , São Paulo State University-UNESP , 14800-060 , Araraquara , SP , Brazil., Najas JZG; Institute of Chemistry , Federal University of Rio de Janeiro-UFRJ , 21940-910 , Rio de Janeiro , RJ , Brazil., Magalhães LG; Computational and Medicinal Chemistry Laboratory, Physics Institute of São Carlos , The University of São Paulo-USP , 13563-120 , São Carlos , SP , Brazil., Bobey AF; Institute of Chemistry , São Paulo State University-UNESP , 14800-060 , Araraquara , SP , Brazil., Mendonça JN; Faculty of Pharmaceutical Sciences of Ribeirão Preto , The University of São Paulo-USP , 14040-903 , Ribeirão Preto , SP , Brazil., Lopes NP; Faculty of Pharmaceutical Sciences of Ribeirão Preto , The University of São Paulo-USP , 14040-903 , Ribeirão Preto , SP , Brazil., Leme FM; Faculty of Pharmaceutical Sciences of Ribeirão Preto , The University of São Paulo-USP , 14040-903 , Ribeirão Preto , SP , Brazil., Teixeira SP; Faculty of Pharmaceutical Sciences of Ribeirão Preto , The University of São Paulo-USP , 14040-903 , Ribeirão Preto , SP , Brazil., Trovó M; Institute of Chemistry , Federal University of Rio de Janeiro-UFRJ , 21940-910 , Rio de Janeiro , RJ , Brazil., Andricopulo AD; Computational and Medicinal Chemistry Laboratory, Physics Institute of São Carlos , The University of São Paulo-USP , 13563-120 , São Carlos , SP , Brazil., Koehbach J; Center for Physiology and Pharmacology , Medical University of Vienna , 1090 , Vienna , Austria.; Institute for Molecular Bioscience , The University of Queensland , 4072 , St. Lucia , Queensland , Australia., Gruber CW; Center for Physiology and Pharmacology , Medical University of Vienna , 1090 , Vienna , Austria., Cilli EM; Institute of Chemistry , São Paulo State University-UNESP , 14800-060 , Araraquara , SP , Brazil., Bolzani VS; Institute of Chemistry , São Paulo State University-UNESP , 14800-060 , Araraquara , SP , Brazil.
Jazyk: angličtina
Zdroj: Journal of natural products [J Nat Prod] 2018 May 25; Vol. 81 (5), pp. 1203-1208. Date of Electronic Publication: 2018 May 14.
DOI: 10.1021/acs.jnatprod.7b00969
Abstrakt: Two new bracelet cyclotides from roots of Pombalia calceolaria with potential anticancer activity have been characterized in this work. The cyclotides Poca A and B (1 and 2) and the previously known CyO4 (3) were de novo sequenced by MALDI-TOF/TOF mass spectrometry (MS). The MS 2 spectra were examined and the amino acid sequences were determined. The purified peptides were tested for their cytotoxicity and effects on cell migration of MDA-MB-231, a triple-negative breast cancer cell line. The isolated cyclotides reduced the number of cancer cells by more than 80% at 20 μM, and the concentration-related cytotoxic responses were observed with IC 50 values of 1.8, 2.7, and 9.8 μM for Poca A (1), Poca B (2), and CyO4 (3), respectively. Additionally, the inhibition of cell migration (wound-healing assay) exhibited that CyO4 (3) presents an interesting activity profile, in being able to inhibit cell migration (50%) at a subtoxic concentration (2 μM). The distribution of these cyclotides in the roots was analyzed by MALDI imaging, demonstrating that all three compounds are present in the phloem and cortical parenchyma regions.
Databáze: MEDLINE
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