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Plinia edulis, popularly known as ‘cambucá’, is used in Brazilian folk medicine to treat several conditions. The aim of this study was to evaluate the mutagenicity and cytotoxicity of cambucá leaf extract, as well as its antioxidant activity. The ‘Ames’ test and Orac assay were used to evaluate the mutagenicity and antioxidant activity, respectively, and the phytochemical analysis of the ethanol leaf extract (LE) was performed by chromatographic and spectrometric methods. The in vitro cytotoxicity was tested on CHO (Chinese Hamster Ovary) cells and on nine human tumor cell lines. Phytochemical analysis of LE has revealed the presence of triterpenes and flavonoids. The LE did not show mutagenicity at the concentration of 20 mg plate-1 and exhibited high antioxidant activity, with Orac value of 3948 µmol TE g-1. The LE and its fractions (ethyl acetate; methanol) showed antiproliferative activity against cancer cell lines and proliferative activity in normal cells. The ethyl acetate fraction was the most active extract, presenting antiproliferative activity against strains of breast cancer, prostate cancer, colon cancer, lung cancer, melanoma and leukemia (GI50 0.01-8.57 µg mL-1), being more effective than the reference drug (doxorubicin) against human breast adenocarcinoma MCF-7 cell line. These results suggest P. edulis as a potential adjuvant in cancer therapy and chemoprevention.

ABSTRACT Gliomas account for the majority of primary malignant brain tumors and present invasive behavior into adjacent healthy tissue. While 4-NC had previously shown to induce apoptotic cell death in a melanoma model, for the glioma model described in this paper 4-NC is cytotoxic for the cells with the induction of the autophagic pathway. Trypan blue exclusion assay showed that 4-NC was cytotoxic in a dose-dependent manner for A172 and T98G cell lines. IC10 and IC50 values were at 32 µM and 41 µM for A172 and T98G respectively. Inhibition of cell proliferation was observed by total cell counts and by cell cycle analysis by flow cytometry, with cell cycle arrest of A172 and T98G cell lines respectively in the G1/G0 and S phases of the cell cycle. 4-NC induced up-regulation of autophagic pathways, as shown by immunoblotting for LC3-I/II, Real-Time PCR for ATG-7 and Beclin-1 genes, and by fluorescence microscopy observation of autophagic vacuoles in cells transfected with GFP-LC3 and electron microscopy. Glioma cells concomitantly treated with 4-NC and 3-MA, an inhibitor of the autophagic process, are more sensible to cell death, suggesting that autophagy protects the cells from the action of 4-NC.

O glaucoma experimental foi produzido em animais como coelho e macaco na tentativa de explicar os mecanismos da doença. Modelos de glaucoma espontâneo também foram descritos. No presente trabalho a elevação da pressão intraocular (PIO) foi produzida em 12 cães por hemácia autóloga fixada em glutaraldcído injetada na câmara anterior do olho esquerdo, sob microscópio cirúrgico. O olho direito foi o controle. Tonometria pelo SchiOtz foi realizada a cada 24 horas com o animal em posição sentada. Com intervalos de tempo que variavam de 2 a 20 dias após a injeção os animais foram sacrificados, os olhos enucleados e congelados, medidos os diâmetros sagital e transversal e então fixados em solução dc formol a 10% c os cortes corados pela hematoxilinaeosina para exame histológico. Em todos os animais a PIO foi maior quando comparado com os controles, o mesmo acontecendo com a medida dos diâmetros que foram também maiores. Os achados histológicos foram compatíveis com glaucoma.