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.
Co-continuousamorphous copolyester (PETG)/ polyoxymethylene (POM) (50/50 wt%/wt%) blends were prepared using a twin screw extruder followed compression molding. Two types of thermoplastic polyurethane (TPU) (i.e., polyester-based and polyether-based) were used to compatibilize the blends system. The thermal properties were characterized by using differential scanning calorimetry (DSC). The mechanical properties of the co-continuous PETG/POM blends were studies through flexural and single-edge notch tensile test (SEN-T). The SEN-T test was performed at three different testing speeds; 1, 100, and 500 mm/min. Scanning electron microscope (SEM) was used to access the fracture surface morphology. The flexural strength of the PETG/POM blends was decreased in the presence of TPU. This was attributed to the elastomeric nature of the TPU. The compatibilizing effects of TPU on the PETG/POM blends were proven by moderate improvement in the fracture toughness and confirmed by the SEM observation. The SEN-T fractured surface of the compatibilized blends showed gross matrix shear yielding as compared to the uncompatibilized system. The K c values of the PETG/ POM blends decreased as the testing speed increased. The optimum toughening effect was observed in PETG/ POM blends compatibilized with polyether-based TPU at testing speed of 100 mm/min. The polyether-based TPU is a more efficient compatibilizer, because the amount required is one-half that of the polyester-based counterpart to achieve the same K c value. This was attributed to the elastomeric nature of the polyether-based TPU. The softer nature of polyether-based TPU could provide better toughening effect than the polyester-based TPU, which is relatively harder in nature. POLYM. ENG. SCI., 45: 710 -719, 2005.
Although noteworthy cell death was reported, DNA fragmentation assay and real-time PCR confirmed that that induced by latex C-serum subfractions was not promoted via the classical apoptotic signalling pathway.
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