Anticancer activity of 7-epiclusianone, a benzophenone from Garcinia brasiliensis, in glioblastoma

Abstract

Background: Glioblastoma 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).

Methods: Cell 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.

Results: Viability 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.

Conclusion: The 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.

Fig. 1

Chemical structure of 7-epiclusianone

Fig. 2

7-epiclusianone treatments inhibit growth and clonogenic capacity. a, b Growth inhibition in U251MG and U138MG cell lines treated with 7-epiclusianone at the indicated concentrations for 48 h (MTS assay); (c-f) 7-epiclusianone potently abrogated the clonogenic capacity of both glioblastoma cell lines (*p < 0.01)

Fig. 3

7-epiclusianone treatments alter cell cycle progression. Cell cycle progression in U251MG (a) and U138MG (b) glioblastoma cell lines after 48 h; c Cyclin A and GAPDH expression after 48 h. *p < 0.01

Fig. 4

7-epiclusianone treatments alter apoptotic rates. a, c-f Increased Annexin V positive cells after treatment with 7-epi-clusianone in glioblastoma (GBM) cells lines; b Increased caspase-3 activation rates after treatment with 7-epiclusianone in GBM cells lines (data are expressed as the mean-SD of all cell lines). *p < 0.05, **p < 0.01. PI, propidium iodide