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The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells


Etti, Imaobong Christopher and Abdullah, Rasedee and Kadir, Arifah and Hashim, Najihah Mohd and Swee, Keong Yeap and Imam, Mustapha Umar and Ramli, Faiqah and Malami, Ibrahim and Kian, Lim Lam and Etti, Ubong and Waziri, Peter and Rahman, Marsitoh (2017) The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells. PLOS ONE, 12 (8). pp. 1-20. ISSN 1932-6203


Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Veterinary Medicine
Institute of Bioscience
DOI Number: https://doi.org/10.1371/journal.pone.0182357
Publisher: Public Library of Science
Keywords: Phytochemicals; Artonin E; Artocarpus elasticus; Breast cancer cell; Cancer
Depositing User: Mohd Hafiz Che Mahasan
Date Deposited: 04 Nov 2018 23:51
Last Modified: 04 Nov 2018 23:51
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1371/journal.pone.0182357
URI: http://psasir.upm.edu.my/id/eprint/63490
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