Melinjo Seeds (Gnetum gnemon L.) Antioxidant Activity and Cytotoxic Effects on MCF-7 Breast Cancer Cells: A Study Based on Tracing of Resveratrol Compound

Abstract

ABSTRACT Introduction: Breast cancer is one of the deadliest cancers worldwide. One of the polyphenols, namely, resveratrol, has been proven to have anticancer activity. Melinjo seeds which contain resveratrol need to be tested for their potential as an anti-breast cancer agent. This study aims to determine the antioxidant activity and cytotoxic effect of melinjo seeds based on solvent variations and resveratrol tracing. Methods: Extraction of melinjo seeds was performed using the soxhletation method. Antioxidant test was performed using the 2,2-diphenyl-1-picrylhydrazil method. The in vitro cytotoxic test was carried out using the microtetrazolium method. Cytotoxic test was carried out on MCF-7 breast cancer cells using a concentration range of melinjo seeds between 31,25 and 1000 μg/mL. Antioxidant and anticancer potentials are expressed in inhibitory concentration (IC)50 values. Resveratrol was traced using preparative high-performance liquid chromatography (Prep-HPLC). Results: Melinjo seed ethanol extract provided the largest total phenolics (126,154 ± 0,865 mg GAE/g sample) and total flavonoids (44,576 ± 0,611 mg QE/g sample) among all solvent fractions. The antioxidant activity of melinjo seeds from ethanol extract, n-hexane fraction, ethyl acetate fraction, and ethanol fraction was 263,307 ppm, 317,595 ppm, 160,878 ppm, and 181,159 ppm, respectively. The ethyl acetate fraction of melinjo seeds showed the strongest cytotoxic effect (94.6 μg/mL) among all extracts and solvent fractions. Prep-HPLC showed that the ethanol extract of melinjo seeds contained resveratrol, while the ethanol and ethyl acetate fractions of melinjo seeds were thought to contain resveratrol derivatives. Conclusion: The antioxidant activity of melinjo seeds showed a cytotoxic effect on MCF-7 cells, which varied based on solvent polarity and total phenolic and total flavonoid. The ethyl acetate fraction which is thought to contain resveratrol derivatives provides the most potent antioxidant activity and cytotoxic effect. These results indicate that melinjo seeds containing resveratrol and its derivatives have the potential for anticancer of the breast. Further studies are still needed in determining the structure of resveratrol compounds and their derivatives to ensure their biological activity and mechanism of action.