Carolina Nor

Antimicrobial activity of some Hypericum species

The crude methanolic extracts of six species of Hypericum [H. caprifoliatum Cham. & Schlecht., H. carinatum Griseb., H. connatum Lam., H. ternum A. St. Hil., H. myrianthum Cham. & Schlecht. and H. polyanthemum Klotzsch ex Reichardt] growing in southern Brazil were analyzed for antimicrobial activity against several microorganisms (bacteria and fungi). The most active plant was H. caprifoliatum, which showed activity against Staphylococcus aureus. Only H. polyanthemum and H. ternum extracts were active against Bacillus subtilis. None of the crude methanolic extracts showed activity against S. epidermidis, Escherichia coli or Saccharomyces cerevisiae. Extracts from these species were evaluated chemically and tannin, flavonoid and phenolic acids were the prominent compounds. The plants contained quercitrin, hyperoside (except H. connatum) and, less frequently, isoquercitrin and chlorogenic acid. In contrast to H. perforatum, which has high concentrations of rutin, these species do not produce this flavonoid or it appears as traces. The tannin concentration varied between 5.1 and 16.7% in H. myrianthum and H. ternum, respectively.

The histone deacetylase inhibitor sodium butyrate promotes cell death and differentiation and reduces neurosphere formation in human medulloblastoma cells.

Increasing evidence suggests that alterations in epigenetic mechanisms regulating chromatin state play a role in the pathogenesis of medulloblastoma (MB), the most common malignant brain tumor of childhood. Histone deacetylase (HDAC) inhibitors, which increase chromatin relaxation, have been shown to display anticancer activities. Here we show that the HDAC inhibitor sodium butyrate (NaB) markedly increases cell death and reduces colony formation in human MB cell lines. In addition, NaB increased the mRNA expression of Gria2, a neuronal differentiation marker, in D283 and DAOY cells and reduced the number of neurospheres in D283 cell cultures. Finally, NaB reduced the viability of D283 cells when combined with etoposide. These data show that NaB displays pronounced inhibitory effects on the survival of human MB cells and suggest that NaB might potentiate the effects of etoposide. In addition, our study suggests that HDAC inhibition might promote the neuronal differentiation of MB cells and provides the first evidence that an HDAC inhibitor might suppress the expansion or survival of MB cancer stem cells.

Inhibitory Activities of Trichostatin A in U87 Glioblastoma Cells and Tumorsphere-Derived Cells

Epigenetic alterations have been increasingly implicated in glioblastoma (GBM) pathogenesis, and epigenetic modulators including histone deacetylase inhibitors (HDACis) have been investigated as candidate therapies. GBMs are proposed to contain a subpopulation of glioblastoma stem cells (GSCs) that sustain tumor progression and therapeutic resistance and can form tumorspheres in culture. Here, we investigate the effects of the HDACi trichostatin A (TSA) in U87 GBM cultures and tumorsphere-derived cells. Using approaches that include a novel method to measure tumorsphere sizes and the area covered by spheres in GBM cultures, as well as a nuclear morphometric analysis, we show that TSA reduced proliferation and colony sizes, led to G2/M arrest, induced alterations in nuclear morphology consistent with cell senescence, and increased the protein content of GFAP, but did not affect migration, in cultured human U87 GBM cells. In cells expanded in tumorsphere assays, TSA reduced sphere formation and induced neuron-like morphological changes. The expression of stemness markers in these cells was detected by reverse transcriptase polymerase chain reaction. These findings indicate that HDACis can inhibit proliferation, survival, and tumorsphere formation, and promote differentiation of U87 GBM cells, providing further evidence for the development of HDACis as potential therapeutics against GBM.