Nat Prod Sci.  2019 Dec;25(4):311-316. 10.20307/nps.2019.25.4.311.

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

• Daud NN
• Septama AW
• Simbak N
• Bakar NH
• Rahmi EP

• KMID: 2468064
• DOI: http://doi.org/10.20307/nps.2019.25.4.311

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 ICâ‚…â‚€ 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.

Keyword

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

MeSH Terms

Apoptosis
Artocarpus*
Cell Line
Cisplatin*
Flavonoids*
MCF-7 Cells*
Medicine, Traditional
Methods
Plants
Cisplatin
Flavonoids

Figure

• 

  Fig. 1 Chemical structure of flavonoids isolated from A. heterophyllus heartwoods, artocarpanone (1), artocarpin (2), cycloartocarpin (3), and cyanomaclurin (4).

• 

  Fig. 2 Isobologram analysis of H460 (a) and MCF-7 (b) when treated with combination of artocarpin and cisplatin.

• 

  Fig. 3 Morphological changes of H460 (a) and MCF-7 (b) induced by cisplatin, artocarpin, and cisplatin-artocapin in combination. Arrows show (CI) Combination Index, (FL) Fluorescence, (AB) Apoptotic Body, (MB) Membrane Blebbing, (EA) Early Apoptosis, (LA) Late Apoptosis, (CC) Chromatin Condensation, (VI) Viable Cells, (DF) DNA Fragmentation.

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