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

Author(s):Show less -

Pinto, Meri Emili F. ^[1] ; Najas, Jhenny Z. G. ^[2] ; Magalhaes, Luma G. ^[3] ; Bobey, Antonio F. ^[1] ; Mendonca, Jacqueline N. ^[4] ; Lopes, Norberto P. ^[4] ; Leme, Flavia M. ^[4] ; Teixeira, Simone P. ^[4] ; Trovo, Marcelo ^[2] ; Andricopulo, Adriano D. ^[3] ; Koehbach, Johannes ^{[5, 6]} ; Gruber, Christian W. ^[5] ; Cilli, Eduardo Maffud ^[1] ; Bolzani, Vanderlan S. ^[1]

Affiliation

^[1] Sao Paulo State Univ, Inst Chem, UNESP, BR-14800060 Araraquara, SP - Brazil

^[2] Fed Univ Rio de Janeiro UFRJ, Inst Chem, BR-21940910 Rio De Janeiro, RJ - Brazil

^[3] Univ Sao Paulo, Phys Inst Sao Carlos, Computat & Med Chem Lab, BR-13563120 Sao Carlos, SP - Brazil

^[4] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[5] Med Univ Vienna, Ctr Physiol & Pharmacol, A-1090 Vienna - Austria

^[6] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072 - Australia

• Document type: Journal article
• Source: Journal of Natural Products; v. 81, n. 5, p. 1203-1208, MAY 2018.
• Web of Science Citations: 6

Abstract

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 MS2 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 mu M, and the concentration-related cytotoxic responses were observed with IC50 values of 1.8, 2.7, and 9.8 mu M 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 mu M). 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. (AU)

• FAPESP's process: 17/17098-4 - Application of MALDI Imaging (MSI) on non-nodulated and nodulated leaves of Psychotria and Hybanthus: Localization, analysis of cyclotides and its relationship with endosymbionts bacteria
• Grantee: Meri Emili Pinto Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC