HIGHLIGHTSd b-catenin activation drives adrenal hyperplasia by blocking cellular differentiation d Upregulation of Pde2a, an inhibitor of cAMP/PKA, is a potential mechanism for the block d Hyperplasia is exacerbated by trophic factor stimulation leading to organomegaly

Propolis is a resin formed by a complex chemical composition of substances that bees collect from plants. Since ancient times, propolis has been used in folk medicine, due to its biological properties, that include antimicrobial, anti-inflammatory, antitumoral and immunomodulatory activities. Glioblastoma is the most common human brain tumor. Despite the improvements in GBM standard treatment, patients’ prognosis is still very poor. The aim of this work was to evaluate in vitro the Tubi-bee propolis effects on human glioblastoma (U251 and U343) and fibroblast (MRC-5) cell lines. Proliferation, clonogenic capacity and apoptosis were analyzed after treatment with 1 mg/mL and 2 mg/mL propolis concentrations for different time periods. Additionally, glioblastoma cell lines were submitted to treatment with propolis combined with temozolomide (TMZ). Data showed an antiproliferative effect of tubi-bee propolis against glioblastoma and fibroblast cell lines. Combination of propolis with TMZ had a synergic anti-proliferative effect. Moreover, propolis caused decrease in colony formation in glioblastoma cell lines. Propolis treatment had no effects on apoptosis, demonstrating a cytostatic action. Further investigations are needed to elucidate the molecular mechanism of the antitumor effect of propolis, and the study of its individual components may reveal specific molecules with antiproliferative capacity.

Background: Impaired apoptosis has been implicated in the development of childhood adrenocortical tumors (ACT), although the expression of apoptosis-related gene expression in such tumors has not been reported. Methods: The mRNA expression levels of the genes CASP3, CASP8, CASP9, FAS, TNF, NFKB, and BCL2 were analyzed by quantitative real-time PCR in consecutive tumor samples obtained at diagnosis from 60 children with a diagnosis of ACT and in 11 non-neoplastic adrenal samples. BCL2 and TNF protein expression was analyzed by immunohistochemistry. Results: A significant association was observed between tumor size R100 g and lower expression levels of the BCL2 (PZ0.03) and TNF (PZ0.05) genes; between stage IV and lower expression levels of CASP3 (PZ0.008), CASP9 (PZ0.02), BCL2 (PZ0.002), TNF (PZ0.05), and NFKB (PZ0.03); Weiss score R3 and lower expression of TNF (PZ0.01); unfavorable event and higher expression values of CASP9 (PZ0.01) and lower values of TNF (PZ0.02); and death and lower expression of BCL2 (PZ0.04). Underexpression of TNF was associated with lower event-free survival in uni-and multivariate analyses (P!0.01). Similar results were observed when patients with Weiss score !3 were excluded. Conclusion: This study supports the participation of apoptosis-related genes in the biology and prognosis of childhood ACT and suggests the complex role of these genes in the pathogenesis of this tumor.

These data suggest that Aurora kinase inhibition may be a target for glioblastoma treatment and could be used as adjuvant to chemo- and radiotherapy.