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CYPERUS ARTICULATUS L. (CYPERACEAE) RHIZOME ESSENTIAL OIL CAUSES CELL CYCLE ARREST IN THE G2/M PHASE AND CELL DEATH IN HEPG2 CELLS AND INHIBITS THE DEVELOPMENT OF TUMORS IN A XENOGRAFT MODEL
Author
Nogueira, Mateus Lima
Lima, Emilly J. S. P. de
Adrião, Asenate A. X.
Fontes, Sheila S.
Silva, Valdenizia Rodrigues
Santos, Luciano de S.
Soares, Milena Botelho Pereira
Dias, Rosane Borges
Rocha, Clarissa Araújo Gurgel
Costa, Emmanoel Vilaça
Silva, Felipe Moura Araujo da
Santos, Marcos André Vannier
Cardozo, Nállarett M. D.
Koolen, Hector Henrique Ferreira
Bezerra, Daniel Pereira
Lima, Emilly J. S. P. de
Adrião, Asenate A. X.
Fontes, Sheila S.
Silva, Valdenizia Rodrigues
Santos, Luciano de S.
Soares, Milena Botelho Pereira
Dias, Rosane Borges
Rocha, Clarissa Araújo Gurgel
Costa, Emmanoel Vilaça
Silva, Felipe Moura Araujo da
Santos, Marcos André Vannier
Cardozo, Nállarett M. D.
Koolen, Hector Henrique Ferreira
Bezerra, Daniel Pereira
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Amazonas State University. Metabolomics and Mass Spectrometry Research Group. Amazonas, MA, Brazil.
Amazonas State University. Metabolomics and Mass Spectrometry Research Group. Amazonas, MA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Clinical Propaedeutics and Integrated Clinical. Bahia, Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Clinical Propaedeutics and Integrated Clinical. Bahia, Salvador, BA, Brazil.
Federal University of Amazonas. Department of Chemistry. Amazonas, MA, Brazil.
Federal University of Amazonas. Department of Chemistry. Amazonas, MA, Brazil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Amazonia Museum. Amazonas, MA, Brazil.
Amazonas State University. Metabolomics and Mass Spectrometry Research Group. Amazonas, MA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Amazonas State University. Metabolomics and Mass Spectrometry Research Group. Amazonas, MA, Brazil.
Amazonas State University. Metabolomics and Mass Spectrometry Research Group. Amazonas, MA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Clinical Propaedeutics and Integrated Clinical. Bahia, Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Clinical Propaedeutics and Integrated Clinical. Bahia, Salvador, BA, Brazil.
Federal University of Amazonas. Department of Chemistry. Amazonas, MA, Brazil.
Federal University of Amazonas. Department of Chemistry. Amazonas, MA, Brazil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Amazonia Museum. Amazonas, MA, Brazil.
Amazonas State University. Metabolomics and Mass Spectrometry Research Group. Amazonas, MA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Abstract
Cyperus articulatus L. (Cyperaceae), popularly known in Brazil as "priprioca" or "piriprioca", is a tropical and subtropical plant used in popular medical practices to treat many diseases, including cancer. In this study, C. articulatus rhizome essential oil (EO), collected from the Brazilian Amazon rainforest, was addressed in relation to its chemical composition, induction of cell death in vitro and inhibition of tumor development in vivo, using human hepatocellular carcinoma HepG2 cells as a cell model. EO was obtained by hydrodistillation using a Clevenger-type apparatus and characterized qualitatively and quantitatively by gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography with flame ionization detection (GC-FID), respectively. The cytotoxic activity of EO was examined against five cancer cell lines (HepG2, HCT116, MCF-7, HL-60 and B16-F10) and one non-cancerous one (MRC-5) using the Alamar blue assay. Cell cycle distribution and cell death were investigated using flow cytometry in HepG2 cells treated with EO after 24, 48 and 72 h of incubation. The cells were also stained with May-Grunwald-Giemsa to analyze the morphological changes. The anti-liver-cancer activity of EO in vivo was evaluated in C.B-17 severe combined immunodeficient (SCID) mice with HepG2 cell xenografts. The main representative substances of this EO sample were muskatone (11.6%), cyclocolorenone (10.3%), α-pinene (8.26%), pogostol (6.36%), α-copaene (4.83%) and caryophyllene oxide (4.82%). EO showed IC50 values for cancer cell lines ranging from 28.5 µg/mL for HepG2 to >50 µg/mL for HCT116, and an IC50 value for non-cancerous of 46.0 µg/mL (MRC-5), showing selectivity indices below 2-fold for all cancer cells tested. HepG2 cells treated with EO showed cell cycle arrest at G2/M along with internucleosomal DNA fragmentation. The morphological alterations included cell shrinkage and chromatin condensation. Treatment with EO also increased the percentage of apoptotic-like cells. The in vivo tumor mass inhibition rates of EO were 46.5-50.0%. The results obtained indicate the anti-liver-cancer potential of C. articulatus rhizome EO.
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