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.
Mateus L NogueiraEmilly J S P de LimaAsenate A X AdriãoSheila S FontesValdenizia R SilvaLuciano de S SantosMilena Botelho Pereira SoaresRosane B DiasClarissa Araújo Gurgel RochaEmmanoel V CostaFelipe M A da SilvaMarcos A Vannier-SantosNállarett M D CardozoHector Henrique Ferreira KoolenDaniel Pereira BezerraPublished in: Molecules (Basel, Switzerland) (2020)
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.
Keyphrases
- cell cycle arrest
- cell death
- gas chromatography
- mass spectrometry
- tandem mass spectrometry
- pi k akt
- cell cycle
- high resolution mass spectrometry
- papillary thyroid
- essential oil
- single cell
- liquid chromatography
- flow cytometry
- squamous cell
- gas chromatography mass spectrometry
- cell therapy
- endothelial cells
- high resolution
- healthcare
- gene expression
- squamous cell carcinoma
- high performance liquid chromatography
- bone marrow
- solid phase extraction
- young adults
- cell free
- early onset
- lymph node metastasis
- drinking water
- ms ms
- induced apoptosis
- climate change
- cross sectional
- childhood cancer
- sensitive detection
- insulin resistance