In vivo and in vitro toxicological evaluations of aqueous extract from Cecropia pachystachya leaves.

CECROPIA PACHYSTACHYA: leaves are popularly used to treat asthma and diabetes. Despite the widespread consumption of this plant, there are few scientific studies regarding its toxicological potential. In order to conduct a thorough study concerning the potential adverse effects, the aim of this study was to assess acute and subacute toxicity tests of crude aqueous extract from C. pachystachya leaves (CAE-Cp) using in vivomodel, as well as in vitro cytotoxicity, genotoxicity and antioxidant activity. In addition, genotoxicity, and cytotoxicity of chlorogenic acid (CGA) and cytotoxicity of isoorientin (ISOO) were also evaluated. The antioxidant activity was verified by DPPH, cytotoxicity using sulforhodamine B (SRB) assay and genotoxicity by comet assay on V79 cells. The phytochemical analysis of CAE-Cp detected flavonoids and tannins, CGA and ISOO as the major compounds utilizing HPLC. The total flavonoid content (6.52 mg/g EQ) and antioxidant activity (EC50 = 62.15 µg/ml) of CAE-Cp were determined. In vitro evaluations with CAE-Cp showed genotoxic effects at 0.31 to 2.5 mg/ml and an expressive cytotoxicity on HT-29 (IC50 = 4.43 µg/ml) cells. CGA was genotoxic against V79 cells at 0.07 mg/ml and cytotoxic against to HT-29 (IC50 = 71.70 µg/ml), OVCAR-3 (IC50 = 80.07 µg/ml), MCF-7 (IC50 = 45.58 µg/ml) and, NCI-H460 (IC50 = 71.89 µg/ml) cancer cell lines. Wistar rats treated with a single dose (2,000 mg/kg) CAE-Cp decreased hemoglobin levels after 14 days, although no significant toxicity was observed in animals after 28 days. In view of the in vitro cytotoxicity and genotoxicity detected, further studies are necessary to establish the safe use of CAE-Cp.

Involvement of ecto-5'-nucleotidase/CD73 in U138MG glioma cell adhesion.

Glioblastoma multiform is the most common and aggressive type of brain tumor. The overexpression of ecto-5'-nucleotidase/CD73 (ecto-5'-NT/CD73), an adhesion molecule and the main enzymatic source of extracellular adenosine, has been reported in tumor cells, and it is emerging as a component of glioma progression. Here, we evaluated the involvement of ecto-5'-NT/CD73 in cell adhesion through its interaction with different components of the extracellular matrix in the human U138MG glioma cell line. The results indicated that adenosine induced an increase in glioma cell adhesion. The treatment of glioma cells with adenosine receptor antagonists, APCP (α,ß-methylene ADP) and dipyridamole prevented the adenosine effect, indicating the participation of extracellular and intracellular signaling pathways in cell adhesion mediated by adenosine. The ECM protein laminin (lam) and chondroitin sulfate (ChS) modulated the ecto-5'-NT/CD73 activity and glioma adhesion in a parallel manner, suggesting the involvement of purinergic signaling in the effects mediated by the extracellular matrix. Taken together, these results suggest that ecto-5'-NT/CD73, an important producer of extracellular adenosine, may modulate glioma cell adhesion and tumor cell-extracellular matrix interactions.