Abstract

Mimosa caesalpiniifolia (Fabaceae) is used by Brazilian people to treat hypertension, bronchitis, and skin infections. Herein, we evaluated the antiproliferative action of the dichloromethane fraction from M. caesalpiniifolia (DFMC) stem bark on murine tumor cells and the in vivo toxicogenetic profile. Initially, the cytotoxic activity of DFMC on primary cultures of Sarcoma 180 (S180) cells by Alamar Blue, trypan, and cytokinesis block micronucleus (CBMN) assays was assessed after 72 h of exposure, followed by the treatment of S180-bearing Swiss mice for 7 days, physiological investigations, and DNA/chromosomal damage. DFMC and betulinic acid revealed similar in vitro antiproliferative action on S180 cells and induced a reduction in viable cells, induced a reduction in viable cells and caused the emergence of bridges, buds, and morphological features of apoptosis and necrosis. S180-transplanted mice treated with DFMC (50 and 100 mg/kg/day), a betulinic acid-rich dichloromethane, showed for the first time in vivo tumor growth reduction (64.8 and 80.0%) and poorer peri- and intratumor quantities of vessels. Such antiproliferative action was associated with detectible side effects (loss of weight, reduction of spleen, lymphocytopenia, and neutrophilia and increasing of GOT and micronucleus in bone marrow), but preclinical general anticancer properties of the DFMC were not threatened by toxicological effects, and these biomedical discoveries validate the ethnopharmacological reputation of Mimosa species as emerging phytotherapy sources of lead molecules.

Highlights

  • Paulo Michel Pinheiro Ferreira,1,2 Renata Rosado Drumond,1,2 Jurandy do Nascimento Silva,1,2 Ian Jhemes Oliveira Sousa,1 Marcus Vinicius Oliveira Barros de Alencar,2,3 Ana Maria Oliveira Ferreira da Mata,2,3 Nayana Bruna Nery Monção,4 Antonia Maria das Graças Lopes Cito,4 Ana Fontenele Urano Carvalho,5 Davi Felipe Farias,6 Patrıcia Marçal da Costa,7 Adriana Maria Viana Nunes,1 João Marcelo de Castro e Sousa,2,3 and Ana Amelia de Carvalho Melo-Cavalcante 2,3

  • We evaluated the antiproliferative action of the dichloromethane fraction from M. caesalpiniifolia (DFMC) stem bark on murine tumor cells and the in vivo toxicogenetic profile

  • The cytotoxic activity of DFMC on primary cultures of Sarcoma 180 (S180) cells by Alamar Blue, trypan, and cytokinesis block micronucleus (CBMN) assays was assessed after 72 h of exposure, followed by the treatment of S180-bearing Swiss mice for 7 days, physiological investigations, and DNA/chromosomal damage

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Summary

Introduction

Paulo Michel Pinheiro Ferreira ,1,2 Renata Rosado Drumond ,1,2 Jurandy do Nascimento Silva ,1,2 Ian Jhemes Oliveira Sousa ,1 Marcus Vinicius Oliveira Barros de Alencar ,2,3 Ana Maria Oliveira Ferreira da Mata ,2,3 Nayana Bruna Nery Monção ,4 Antonia Maria das Graças Lopes Cito ,4 Ana Fontenele Urano Carvalho ,5 Davi Felipe Farias ,6 Patrıcia Marçal da Costa ,7 Adriana Maria Viana Nunes ,1 João Marcelo de Castro e Sousa ,2,3 and Ana Amelia de Carvalho Melo-Cavalcante 2,3. S180-transplanted mice treated with DFMC (50 and 100 mg/kg/day), a betulinic acid-rich dichloromethane, showed for the first time in vivo tumor growth reduction (64.8 and 80.0%) and poorer peri- and intratumor quantities of vessels Such antiproliferative action was associated with detectible side effects (loss of weight, reduction of spleen, lymphocytopenia, and neutrophilia and increasing of GOT and micronucleus in bone marrow), but preclinical general anticancer properties of the DFMC were not threatened by toxicological effects, and these biomedical discoveries validate the ethnopharmacological reputation of Mimosa species as emerging phytotherapy sources of lead molecules. Ey reported that ethanolic extracts of different parts of M. caesalpiniifolia (leaves, bark, fruit, and inflorescences) cause vasorelaxation, the tea of flowers promotes hypotension and tachycardia, and the ethanolic extract causes hypotension and bradycardia [22] Based on these ethnopharmacological properties, this work evaluated the antiproliferative action of the dichloromethane fraction from M. caesalpiniifolia (DFMC) stem bark on murine tumor cells and the in vivo toxicogenetic profile

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