Paulo Luiz de Sá Júnior1, Diana Aparecida Dias Câmara2, André Santos Costa3, Jorge Luis Maria Ruiz4, Débora Levy4, Ricardo Alexandre Azevedo5, Kerly Fernanda Mesquita Pasqualoto6, Camila Fávero de Oliveira3, Thatiana Corrêa de Melo3, Nara Diniz Soares Pessoa7, Pâmela Maria Moreira Fonseca8, Alexandre Pereira3, Rodrigo Pinheiro Araldi3, Adilson Kleber Ferreira5. 1. Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil, . Electronic address: paulsaj2001@yahoo.com.br. 2. Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil, ; Morphology and Genetics Department, Universidade Federal de Sao Paulo, SP, Brazil. 3. Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil. 4. Laboratory of Genetics and Molecular Hematology (LIM31), University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil. 5. Departament of Immunology, Laboratory of Tumor Immunology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, SP, Brazil. 6. Biochemistry and Biophysics Laboratory, Butantan Institute, Sao Paulo, SP, Brazil. 7. Programa de Pós-graduação em Ciências da Saúde, Faculdade de Ciências Médicas, Universidade de Pernambuco (UPE). 8. Camilo Castelo Branco University, Department of Biomedical Instrumentation, Biomedical Engineering Center, Sao Jose dos Campos, Sao Paulo, SP, Brazil.
Abstract
BACKGROUND: Eugenol (EUG) is a major phenolic compound present in clove whose anti-cancer properties have been demonstrated previously. These anti-cancer properties may involves the modulation of different mechanisms, including α-estrogen receptor (αER) in luminal breast cancer cells, COX-2 inhibition in melanoma cells or p53 and caspase-3 activation in colon cancer cells. HYPOTHESIS: EUG promotes a burst in ROS production causing cell-cycle perturbations, mitochondria toxicity and clastogenesis triggering apoptosis in melanoma breast- and cervix-cancer cells in vitro. METHODS: Morphological changes were evaluated through the light- and electronic- microscopy. Cell-cycle, ROS, PCNA and Apoptosis was detected by flow cytometry and clastogenicity was evaluated by Comet-assay. RESULTS: The results obtained herein pointed out that EUG promotes, increasing ROS production leading to abrogation of G2/M of phase of cell-cycle, and consecutively, clastogenesis in vitro. In addition, EUG induces Proliferation Cell Nuclear Antigen (PCNA) downregulation and decreasing in mitochondria potential (ΔΨm). Of note, a Bax up-regulation was also observed on cells treated with EUG. All of these findings cooperate in order to induce apoptosis in cancer cells. CONCLUSION: These promising results presented herein shed new light on the mechanisms of action of EUG suggesting a possible applicability of this phenylpropanoid as adjuvant in anti-cancer therapy.
BACKGROUND:Eugenol (EUG) is a major phenolic compound present in clove whose anti-cancer properties have been demonstrated previously. These anti-cancer properties may involves the modulation of different mechanisms, including α-estrogen receptor (αER) in luminal breast cancer cells, COX-2 inhibition in melanoma cells or p53 and caspase-3 activation in colon cancer cells. HYPOTHESIS: EUG promotes a burst in ROS production causing cell-cycle perturbations, mitochondria toxicity and clastogenesis triggering apoptosis in melanoma breast- and cervix-cancer cells in vitro. METHODS: Morphological changes were evaluated through the light- and electronic- microscopy. Cell-cycle, ROS, PCNA and Apoptosis was detected by flow cytometry and clastogenicity was evaluated by Comet-assay. RESULTS: The results obtained herein pointed out that EUG promotes, increasing ROS production leading to abrogation of G2/M of phase of cell-cycle, and consecutively, clastogenesis in vitro. In addition, EUG induces Proliferation Cell Nuclear Antigen (PCNA) downregulation and decreasing in mitochondria potential (ΔΨm). Of note, a Bax up-regulation was also observed on cells treated with EUG. All of these findings cooperate in order to induce apoptosis in cancer cells. CONCLUSION: These promising results presented herein shed new light on the mechanisms of action of EUG suggesting a possible applicability of this phenylpropanoid as adjuvant in anti-cancer therapy.
Authors: Mariam A Fouad; Mohamed M Sayed-Ahmed; Etimad A Huwait; Hafez F Hafez; Abdel-Moneim M Osman Journal: BMC Pharmacol Toxicol Date: 2021-01-28 Impact factor: 2.483
Authors: Oana M Aburel; Ioana Z Pavel; Maria D Dănilă; Theia Lelcu; Alexandra Roi; Rodica Lighezan; Danina M Muntean; Laura C Rusu Journal: Oxid Med Cell Longev Date: 2021-03-02 Impact factor: 6.543