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.
Highlights
Natural products are an important source of new drugs for a wide range of diseases
The essentialessential oil (EO) recovery from rhizome of C. articulatus was 0.58 ± 0.04% (w/w), in which a composition dominated by terpenoids was observed (Table 1)
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 after 72 h of incubation (Table 2)
Summary
Natural products are an important source of new drugs for a wide range of diseases. In the latest review of natural medicines published by DJ Newman and GM Cragg of the National Institutes of Health (United States of America), they reported that 76.4% of all new drugs approved by the FDA from 1981 to 2019 (n = 1881) are natural products or natural-based components [1]. Some plant-derived drugs are among the most important antineoplastic agents, including the family of vinca alkaloids isolated from Catharanthus roseus G. In African and American countries, C. articulatus rhizomes are used in popular medical practices to treat many disorders, including infections, fevers, pain, seizures, gastrointestinal and urinary disorders, bleeding, irregular menstruation, cancer, and as an abortion agent/contraceptive [5,6,7,8,9,10,11,12]. People in the Amazon grind or suck the rhizome with water to drink. It is sold in herbal medicine stores in the USA and South America as a fluid extract or in capsules [6]
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