Antitumor Effect of Guatteria olivacea R. E. Fr. (Annonaceae) Leaf Essential Oil in Liver Cancer

Abstract

Guatteria olivacea R. E. Fries (synonym Guatteria punctata (Aubl.) R.A. Howard) is a tree of 10–27 m tall popularly known as “envira-bobó”, “envira-fofa”, “envireira”, “embira”, “embira-branca”, “embira-preta”, envira-branca”, and “envira-preta”, which can be found in the Brazilian Amazon biome. In this study, we evaluated the cytotoxic and antitumor effects of the essential oil (EO) obtained from the leaves of G. olivacea against liver cancer using HepG2 cells as a model. EO was obtained using a hydrodistillation Clevenger-type apparatus and was qualitatively and quantitatively characterized using GC–MS and GC–FID, respectively. The alamar blue assay was used to assess the cytotoxic potential of EO in a panel of human cancer cell lines and human non-cancerous cells. In HepG2 cells treated with EO, YO-PRO-1/propidium iodide staining, cell cycle distribution, and reactive oxygen species (ROS) were examined. In C.B-17 SCID mice with HepG2 cell xenografts, the efficacy of the EO (20 and 40 mg/kg) was tested in vivo. GC–MS and GC–FID analyses showed germacrene D (17.65%), 1-epi-cubenol (13.21%), caryophyllene oxide (12.03%), spathulenol (11.26%), (E)-caryophyllene (7.26%), bicyclogermacrene (5.87%), and δ-elemene (4.95%) as the major constituents of G. olivacea leaf EO. In vitro cytotoxicity of EO was observed, including anti-liver cancer action with an IC50 value of 30.82 μg/mL for HepG2 cells. In HepG2 cells, EO treatment increased apoptotic cells and DNA fragmentation, without changes in ROS levels. Furthermore, the EO inhibited tumor mass in vivo by 32.8–57.9%. These findings suggest that G. olivacea leaf EO has anti-liver cancer potential.

Duguetia pycnastera Sandwith (Annonaceae) Leaf Essential Oil Inhibits HepG2 Cell Growth In Vitro and In Vivo

“…EOs showing IC 50 values lower than 30 μg/mL in cell viability assays using tumor cell lines are considered promising in our cytotoxic compound screening program [ 18 , 19 , 20 ]. Interestingly, D. pycnastera leaf EO had IC 50 values lower than 30 μg/mL for many of the cell lines tested and was chosen for future experiments.…”

“…leaf EO also caused DNA fragmentation and cell death by apoptosis in HepG2 cells. Interestingly, germacrene D, bicyclogermacrene, and spathulenol are among its main components [ 18 ]. The EO extracted from Annona squamosa L. pericarps presented spathulenol as its major chemical component and induced apoptosis in SMMC-7721 liver cancer cells [ 25 ].…”

“…Previously, the leaf EO of D. gardneriana was tested in vivo on B16-F10 tumor-bearing C57BL/6 mice and found to reduce tumor growth by 5.4 and 37.5% at doses of 40 and 80 mg/kg, respectively [ 6 ]. In the Annonaceae family, HepG2-bearing C.B-17 SCID mice treated with G. olivacea leaf EO at doses of 20 and 40 mg/kg showed tumor reduction rates of 32.8–57.9% [ 18 ]. A. vepretorum leaf EO reduced the growth of B16-F12 in vivo by 34.46% at the dose of 50 mg/kg, which was increased to 62.66% when the EO was microencapsulated in β-cyclodextrin [ 24 ].…”

“…A Shimadzu GC-17A GC system with a DB-5MS capillary column (30 m × 0.25 mm × 0.25 μm) was used for gas chromatography with flame ionization detection (GC-FID) analysis, and a Trace Ultra gas chromatograph system coupled to an ISQ single quadrupole mass spectrometer (Thermo Scientific, Waltham, MA, USA) was used for gas chromatography with mass spectrometry (GC–MS) detection analysis, both according to our previous work [ 18 , 30 ].…”

Research Progress on Sesquiterpene Compounds from Artabotrys Plants of Annonaceae

“…The chemical diversity present in Annonaceae species is vast, yielding a plethora of natural compounds such as alkenes [4], terpenoids [5], alkaloids [6][7][8][9][10], and phenols [11]. These compounds demonstrate a broad spectrum of pharmacological activities, including anti-mosquito [12], anti-cancer [13][14][15], antibacterial [16], anti-protozoal [17,18], and antifungal [19]. Among them, Annonaceous acetogenins stand out for their potent anti-tumor potential, making them one of the most promising natural product discoveries [20].…”