Abstract
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.
Highlights
Breast cancer is a complex and heterogeneous disease, constituting an enormous burden to the world at large with increasing mortality rates
The growth inhibitory effect of Artonin E was investigated on MDA-MB 231 breast cancer cells as well as on the normal breast epithelial cells
The acridine orange (AO) and propidium iodide (PI) double staining analysis revealed the morphology of apoptosis in Artonin E-treated MDA-MB 231 breast cancer
Summary
Breast cancer is a complex and heterogeneous disease, constituting an enormous burden to the world at large with increasing mortality rates. It is the most frequently diagnosed cancer and the leading cause of cancer death among women [1] with an estimated 1.67 million new cases diagnosed in the year 2012 [2]. Notable among breast cancer cases, are the triple negative breast cancers These cancers are highly aggressive by nature and are characterized by the absence of hormone receptors [9]. This flurry encouraged the search into natural sources for relatively safe alternatives to ameliorate the clinical consequences of the hormone negative breast cancer
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