β-Carboline-α-aminophosphonate Derivative: A Promising Antitumor Agent for Breast Cancer Treatment
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Published:2023-05-08
Issue:9
Volume:28
Page:3949
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Zani Caroline Pinto1, Zani Aline Pinto1, Thomazini Cristiane Melissa1, Retamiro Karina Miyuki1, de Oliveira Aline Rufino2, Gonçalves Débora Laís2, Sarragiotto Maria Helena2, Garcia Francielle Pelegrin1ORCID, de Oliveira Silva Sueli1ORCID, Nakamura Celso Vataru1ORCID, Ueda-Nakamura Tania1ORCID
Affiliation:
1. Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil 2. Department of Chemistry, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil
Abstract
Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments available, we analyzed the in vitro cytotoxic potential of ((4-Fluoro-phenyl)-{2-[(1-phenyl-9H-β-carboline-3-carbonyl)-amino]-ethylamino}-methyl)-phosphonic acid dibutyl ester (BCP-1) in breast cancer cells (MCF-7 and MDA-MB-231) and in a non-tumor breast cell line (MCF-10A). BCP-1 has an α-aminophosphonate unit linked to the β-carboline nucleus, and the literature indicates that compounds of these classes have high biological potential. In the present study, the mechanism of action of BCP-1 was investigated through methods of spectrofluorimetry, flow cytometry, and protein expression analysis. It was found that BCP-1 inhibited the proliferation of both cancer cell lines. Furthermore, it induced oxidative stress and cell cycle arrest in G2/M. Upregulation of apoptosis-related proteins such as Bax, cytochrome C, and caspases, as well as a decrease in the anti-apoptotic protein Bcl-2, indicated potential induction of apoptosis in the MDA-MB-231 cells. While in MCF-7 cells, BCP-1 activated the autophagic death pathway, which was demonstrated by an increase in autophagic vacuoles and acidic organelles, in addition to increased expression of LC3I/LC3II and reduced SQSTM1/p62 expression. Further, BCP-1 demonstrated antimetastatic potential by reducing MMP-9 expression and cell migration in both breast cancer cell lines. In conclusion, BCP-1 is a promising candidate for breast cancer chemotherapy.
Funder
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Financiadora de Estudos e Projetos PRONEX/Fundação Araucária Conselho Nacional de Desenvolvimento Científico e Tecnológico
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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