Abstract
BackgroundGlioblastoma is the most common tumor of the central nervous system and one of the hardest tumors to treat. Consequently, the search for novel therapeutic options is imperative. 7-epiclusianone, a tetraprenylated benzophenone isolated from the epicarp of the native plant Garcinia brasiliensis, exhibits a range of biological activities but its prospect anticancer activity is underexplored. Thus, the aim of the present study was to evaluate the influence of 7-epiclusianone on proliferation, clonogenic capacity, cell cycle progression and induction of apoptosis in two glioblastoma cell lines (U251MG and U138MG).MethodsCell viability was measured by the MTS assay; for the clonogenic assay, colonies were stained with Giemsa and counted by direct visual inspection; For cell cycle analysis, cells were stained with propidium iodide and analyzed by cytometry; Cyclin A expression was determined by immunoblotting; Apoptotic cell death was determined by annexin V fluorescein isothiocyanate labeling and Caspase-3 activity in living cells.ResultsViability of both cell lines was drastically inhibited; moreover, the colony formation capacity was significantly reduced, demonstrating long-term effects even after removal of the drug. 7-epiclusianone treatment at low concentrations also altered cell cycle progression, decreased the S and G2/M populations and at higher concentrations increased the number of cells at sub-G1, in concordance with the increase of apoptotic cells.ConclusionThe present study demonstrates for the first time the anticancer potential of 7-epiclusianone against glioblastoma cells, thus meriting its further investigation as a potential therapeutic agent.
Highlights
Glioblastoma is the most common tumor of the central nervous system and one of the hardest tumors to treat
Isolation and characterization of 7-epiclusianone The fruits of Garcinia brasiliensis, after identification of plant material by Dr João Augusto Alves Meira Neto, were collected from trees growing under controlled conditions at the herbarium of the Federal University of Viçosa – UFV, Minas Gerais state, Brazil, where the voucher specimen (#VIC2604) is deposited
Evaporation of the solvent under reduced pressure at 45 °C afforded the crude EtOH extract, which was chromatographed on silica gel (230–400 mesh) column and eluted with crescent polarity mixtures of (n-hexane, n-hexane-ethyl acetate (95:5), n-hexane-ethyl acetate (80:20), n-hexane-ethyl acetate (50:50), n-hexane-ethyl acetate (20:80) and ethanol) to give 25 fractions. These fractions were pooled into four groups according to their similarities after the analysis using thin layer chromatography (TLC) and compared to the standard 7-epiclusianone previously isolated
Summary
Glioblastoma is the most common tumor of the central nervous system and one of the hardest tumors to treat. 7-epiclusianone, a tetraprenylated benzophenone isolated from the epicarp of the native plant Garcinia brasiliensis, exhibits a range of biological activities but its prospect anticancer activity is underexplored. Glioblastoma (GBM) is the most aggressive and common glial tumors, and it represents the main type of primary cancer of the central nervous system in adults [1]. GBM remains as one of the hardest tumors to treat, making search for novel therapeutic options imperious. Among the variety of plant extracts described so far, 7-epiclusianone, a tetraprenylated benzophenone isolated from the epicarp of the native plant Garcinia brasiliensis (commonly known as bacupari), has traditionally been used in the folk medicine for the treatment of different diseases [6]
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