EFEITO ANTICÂNCER IN VIVO E IN VITRO DO ÓLEO ESSENCIAL EXTRAÍDO DA FOLHA DA GUAVIRA

Abstract

Campomanesia adamantium is a native species of the Brazilian Cerrado. Known as a natural source of phenolic compounds, it has promising biological activities. The aim of this study was to evaluate the in vitro activity of the essential oil from guavira leaves against immortalized non-tumor cell lines and tumor cell lines, as well as in vivo, using the experimental model of murine melanoma in BALB/C mice. The essential oil was extracted by hydrodistillation and its chemical composition was determined by gas chromatography coupled to mass spectrometry (GC/MS). The cytotoxic activity of the essential oil was evaluated in vitro in neoplastic B16F10 cell lines and in normal cells (murine 3T3 fibroblasts and human umbilical cord endothelial cells - HUVEC). For the development of the hypodermic nodule, suspensions of B16F10 cells were inoculated subcutaneously in the interscapular region of the animals. On the 10th day after inoculation, the animals were distributed into groups: Group 1 (Control, only B16F10 cells), Groups 2 and 3 (guavira essential oil via Gavage 200 and 300mg/kg), Groups 4 and 5 (guavira essential oil via I.P 200 and 300ug/ml), Group 6 (Doxorubicin 5mg/kg), Group 7 (guavira essential oil via (I.P 45mg/ml) and Group 8 (guavira essential oil 3%, topical). The acute toxicity of the guavira leaf essential oil was based on the OECD (Organization for Economic Co-operation and Development) Guidelines 423. The results obtained in the chemical profile indicated 32 substances in the essential oil. Bicyclogermacrene (16.86%), linalool (7.01%), germacrene D (7.14%), E-caryophyllene (6.38%), limonene (5. -terpineol (4.70%) appeared in the highest percentage. The oil showed low cytotoxicity, with GI50 < 250 μg/mL (concentration capable of inhibiting 50% of cell growth), and for the neoplastic lineage B16F10, the GI50 found was 2.85 μg/mL. The selectivity index, which indicates how many times the oil was selective for the neoplastic lineage, was 87.71, indicating high selectivity of the oil. In the in vivo assay, the groups treated via gavage (300 mg/kg) and topical (3%) showed a reduction in tumor weight when compared to the control (Group 1) of 87.56% and 87.93%, respectively. In the acute oral toxicity assay, there were clearly evident signs of intoxication at the highest dose (2000 mg/kg). Mice treated with 300 mg/kg showed moderate signs of intoxication, however, at doses of 50 mg/kg and 5 mg/kg there was no change in behavior, indicating low toxicity.