Synergistic Effect of Flavonoids fromArtocarpus heterophyllusHeartwoods on Anticancer Activity of Cisplatin Against H460 and MCF-7 Cell Lines

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 IC 50 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.

The Role of Artocarpin In Inhibiting Wnt/Β-Catenin Signalling Pathway Through Its Binding to Tcf-4/Β-Catenin Complex in H460-Derived Lung Cancer Stem Cells

“…This result further supports the previous findings on the anticancer activity of this compound on various cancer cell lines, including human leukaemia HL-60 (CCL-240) cells, colorectal adenocarcinoma HT-29 (HTB38) cells, breast adenocarcinoma cancer MCF-7 (HTB-22) cell, and non-small lung cancer H460 (HTB-177) cell lines (Daud et al, 2019;Mat Daud et al, 2021). Furthermore, in H460, artocarpin displayed antiproliferation, antidifferentiation, antimigration, and anti-invasion capabilities (Daud et al, 2020).…”

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“…This result further supports the previous findings on the anticancer activity of this compound on various cancer cell lines, including human leukaemia HL-60 (CCL-240) cells, colorectal adenocarcinoma HT-29 (HTB38) cells, breast adenocarcinoma cancer MCF-7 (HTB-22) cell, and non-small lung cancer H460 (HTB-177) cell lines (Daud et al, 2019;Mat Daud et al, 2021). Furthermore, in H460, artocarpin displayed antiproliferation, antidifferentiation, antimigration, and anti-invasion capabilities (Daud et al, 2020).…”

Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy

“…The mechanism of flavonoid's action in potentiating cisplatin treatment is depletion of the cellular oxidative machinery, aiding mitochondrial dysfunction and thus leading to apoptosis [144]. A few more examples of flavonoids, such as artocarpanone, artocarpin, cycloartocarpin, and cyanomaclurin, extracted from Artocarpus heterophyllus heartwoods have a synergistic effect with cisplatin on non-small lung and breast cancers [145]. Recent studies have shown that quercetin prevented cisplatin nephrotoxicity by ameliorating tubular damage [146].…”