ANTITUMORAL POTENTIAL OF VARRONIA CURASSAVICA JACQ. ESSENTIAL OILS

Abstract

Introduction: Cancer is a disease that affects a large portion of the world's population and represents a public health problem. In Brazil, this disease is the second biggest cause of mortality. Despite this, most available chemotherapy drugs can achieve unsatisfactory results for the treatment of carcinomas and present high systemic toxicity. Given the need for new molecules with antitumor activity, numerous studies have been carried out. The plant Varronia curassavica Jacq. is a Brazilian medicinal and aromatic plant that has been used both in popular medicine and in the pharmaceutical industry for its anti-inflammatory action. Recent studies have shown that the extract of this plant has antitumor potential, however no reports were found for its essential oil. Essential oils are complex mixtures of volatile compounds, with their bioactivity normally attributed to their majority compound. Objective: the objective of the present work is to evaluate the antitumor potential of V. curassavica essential oils from 6 chemical groups. Methodology: one plant from each chemical group was selected and its essential oil was extracted by hydrodistillation. The extracted oils were chemically analyzed by gas chromatography with mass spectrometry and flame ionization. The in vitro cytotoxicity of essential oils was tested on tumor cells of ATCC human hepatocellular carcinoma, human colon carcinoma and human fibroblasts using the alamar blue method. Results: In the chemical analysis of the six selected oils, the main compounds were identified as α-pinene, sabinene, E-caryophyllene, bicyclogermacrene, shyobunone IV, germacrene D-4-ol, 5-methyl-9-methylene-2-isopropylcyclodec-4 -en-1-one, α-turmerone and shyobunol. Some of these compounds do not yet have antitumor activity reported in the literature. All samples were tested at a concentration of 50µg/mL and at this concentration they showed inhibition of over 80% of tumor cells, demonstrating efficiency similar to the positive control. When estimating the IC50 for human tumor cells and fibroblasts, the oil from chemical group 3 was the one that presented the lowest IC50 (6.86 μg/mL) for human colon carcinoma, its major compounds are respectively 5-methyl-9-methylene -2-isopropylcyclodec-4-en-1-one, α-turmerone and E-caryophyllene. However, chemical group 4 was the essential oil that demonstrated consistent antitumor activity against both types of carcinoma tested, human colon carcinoma (11.87 μg/mL) and human hepatocellular carcinoma (10.43 μg/mL), however this oil was not selective as it also presented IC50 (12.42 μg/mL) for fibroblasts. This oil's main compounds are germacrene D-4-ol and shyobunol respectively. The essential oil from group 1 was the most selective for tumor cells as it presented the highest IC50 for human fibroblasts (27.63 μg/mL). Conclusion: the present study demonstrated that the essential oils of Varronia curassavica Jacq. showed cytotoxicity to tumor cells. Most of the major compounds found in the oils studied do not have antitumor activity reported in the literature, which suggests new natural molecules with antitumor potential, such as germacrene D-4-ol and shyobunol, in order to serve as a basis for the development of future chemotherapy drugs.