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Synergistic Effect of Flavonoids from Artocarpus heterophyllus Heartwoods on Anticancer Activity of Cisplatin Against H460 and MCF-7 Cell Lines

Natural Product Sciences 2019년 25권 4호 p.311 ~ 316
 ( Daud Nik Nurul Najihah Nik Mat ) - Universiti Sultan Zainal Abidin Faculty of Medicine

 ( Septama Abdi Wira ) - Indonesian Institute of Sciences Research Center for Chemistry
 ( Simbak Nordin ) - Universiti Sultan Zainal Abidin Faculty of Medicine
 ( Bakar Nor Hidayah Abu ) - Universiti Sultan Zainal Abidin Faculty of Medicine
 ( Rahmi Eldiza Puji ) - UPN Veteran Faculty of Medicine

Abstract


Artocarpus heterophyllus has been used as traditional medicine. This plant is one of the sources of flavonoid. Flavonoid compounds possessed a wide range of biological properties including anticancer. This study was performed to investigate the cytotoxic effect of flavonoids from A. heterophyllus on H460 and MCF-7 cell lines. The interaction of flavonoids and cisplatin against tested cancer cells was also evaluated. MTT assay was used to determine the cytotoxic effect of flavonoid. Isobologram analysis was selected to evaluate the synergistic effect between flavonoid and cisplatin, their interaction was then confirmed using AO/PI staining method. Amongst of flavonoid compounds, artocarpin exhibited strong cytotoxic effect on both MCF-7 and H460 cell lines with IC50 values of 12.53 μg/mL (28.73 μM) and 9.77 μg/mL (22.40 μM), respectively. This compound enhanced anticancer activity of cisplatin against H460 and MCF-7. The combination produced a synergistic effect on H460 and MCF-7 cell lines with a combination index (CI) values of 0.2 and 0.18, respectively. The AO/ PI stained demonstrated that the combination of artocarpin and cisplatin caused morphological changes that indicated apoptosis. Moreover, artocarpanone also significantly increased cytotoxic effect of cisplatin compared to its single concentration with CI below than 1. This result suggested the potency of flavonoid named artocarpin to enhance the anticancer activity of cisplatin on H460 and MCF-7 cell lines.

키워드

Artocarpus heterophyllus; artocarpin; non-small lung cancer cell; breast cancer cell; cytotoxicity; synergistic
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