Dados do Trabalho

Título

THE ANTICANCER AND BIOLOGICAL ROLE OF R-CARVONE AND ALPHA-PHELLANDRENE

Introdução

Alternatives to the ongoing cancer treatments are extremely important and highlighted nowadays in order to improve patient’s quality of life by reducing induced limitations and adverse effects. Accordingly, natural compounds have an important role since they may present anticancer effects associated with less toxicity; in this context, monoterpenes show themselves as a promising alternative.

Objetivo

Thereby, this study aims to investigate the antitumor activity and the induced effects of two monoterpenes, the R-carvone (CRV) and the alpha-phellandrene (PLD), in vivo, using Ehrlich’s breast cancer model.

Método

For that, female Swiss mice were treated with these compounds, individually or in combination with methotrexate (MTX – a chemotherapy agent). Over 21 days, the size of the tumors was measured and, after this time, the animals were euthanized and their tumors and blood were collected for further analysis. Part of the tumor was used for histological analysis and from the other part it was extracted the RNA to evaluate gene expression.

Resultado

There was a reduction in the growth, final volume, and final weight of the tumors in all treated groups, with the CRV group presenting very similar results to the positive control group (treated with MTX alone), while the association of CRV+MTX showed enhanced anticancer activity. Hematological and biochemical analyses of the blood were compared both to negative control and naive mice and showed little alterations in the treated groups, mainly related to white cell increase. Histological analysis showed enhanced tumor necrosis for the CRV group, while PLD decreased this parameter; on the other hand, both the monoterpenes reduced the inflammation in the tumor microenvironment and increased the mitosis count. Treated tumors also presented changes in gene expression, showing a pattern of increase of anti-inflammatory, antioxidant, adhesion, death, and signal transduction-related genes, and a decrease in angiogenesis and extracellular matrix degradation-related genes; CRV induced a reduction of one more angiogenesis-related gene, while PLD was shown to increase significantly the expression of an apoptosis-related gene, both corroborating the histological findings.

Conclusão

Altogether, these results indicate that both the monoterpenes are promising adjuvants in breast cancer treatment, presenting significant anticancer activity, low toxicity, and acting by different biological pathways; the CRV, in turn, was capable of enhancing the chemotherapy.

Palavras-chave

Breast cancer; monoterpenes; natural compounds.