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ß-Carboline-α-aminophosphonate Derivative: A Promising Antitumor Agent for Breast Cancer Treatment.
Zani, Caroline Pinto; Zani, Aline Pinto; Thomazini, Cristiane Melissa; Retamiro, Karina Miyuki; de Oliveira, Aline Rufino; Gonçalves, Débora Laís; Sarragiotto, Maria Helena; Garcia, Francielle Pelegrin; de Oliveira Silva, Sueli; Nakamura, Celso Vataru; Ueda-Nakamura, Tania.
Afiliação
  • Zani CP; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Zani AP; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Thomazini CM; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Retamiro KM; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • de Oliveira AR; Department of Chemistry, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Gonçalves DL; Department of Chemistry, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Sarragiotto MH; Department of Chemistry, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Garcia FP; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • de Oliveira Silva S; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Nakamura CV; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
  • Ueda-Nakamura T; Laboratory of Technological Innovation in the Development of Pharmaceuticals and Cosmetics, State University of Maringá, Maringá CEP 87020-900, Paraná, Brazil.
Molecules ; 28(9)2023 May 08.
Article em En | MEDLINE | ID: mdl-37175359
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-ß-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 ß-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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Antineoplásicos Limite: Female / Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Antineoplásicos Limite: Female / Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça