No abstract

No abstract

Abstract. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells. However, sensitivity of cancer cells for induction of apoptosis by TRAIL varies considerably. Therefore, it is important to develop agents that overcome this resistance. We show, for the first time, that eupatolide, the sesquiterpene lactone isolated from the medicinal plant Inula britannica, sensitizes human breast cancer cells to TRAIL-induced apoptosis. Treatment with TRAIL in combination with subtoxic concentrations of eupatolide enhanced the TRAILinduced cytotoxicity in MCF-7, MDA-MB-231 and MDA-MB-453 breast cancer cells, whereas each reagent alone slightly induced cell death. The combination induced sub-G 1 phase DNA content and annexin V-staining in MCF-7 cells, which are major features of apoptosis. Apoptotic characteristics induced by the combined treatment were significantly inhibited by a pan-caspase inhibitor. The sensitization to TRAIL-induced apoptosis was accompanied by the activation of caspase-8 and was concomitant with Bid and poly(ADP-ribose) polymerase (PARP) cleavage. Treatment of eupatolide alone significantly down-regulated the expression of cellular FLICE inhibitory protein (c-FLIP) in MCF-7 cells. Furthermore, enforced expression of c-FLIP significantly attenuated the apoptosis induced by this combination in MCF-7 cells, suggesting a key role for c-FLIP down-regulation in these events. We also observed that euaptolide inhibited AKT phosphorylation in a dose-and time-dependent manner. Moreover, inhibition of Akt by LY294002, a specific PI3K inhibitor, down-regulated c-FLIP expression in MCF-7 cells. Taken together, these results indicate that eupatolide could augment TRAIL-induced apoptosis in human breast cancer cells by down-regulating c-FLIP expression through the inhibition of AKT phosphorylation and be a valuable compound to overcome TRAIL resistance in breast cancer cells.

Rice straw is closely associated with meju fermentation and it is generally known that the rice straw provides meju with many kinds of microorganisms. In order to elucidate the origin of meju fungi, the fungal diversity of rice straw was examined. Rice straw was collected from 12 Jang factories where meju are produced, and were incubated under nine different conditions by altering the media (MEA, DRBC, and DG18), and temperature (15°C, 25°C, and 35°C). In total, 937 strains were isolated and identified as belonging to 39 genera and 103 species. Among these, Aspergillus, Cladosporium, Eurotium, Fusarium, and Penicillium were the dominant genera. Fusarium asiaticum (56.3%), Cladosporium cladosporioides (48.6%), Aspergillus tubingensis (37.5%), A. oryzae (31.9%), Eurotium repens (27.1%), and E. chevalieri (25.0%) were frequently isolated from the rice straw obtained from many factories. Twelve genera and 40 species of fungi that were isolated in the rice straw in this study were also isolated from meju. Specifically, A. oryzae, C. cladosporioides, E. chevalieri, E. repens, F. asiaticum, and Penicillium polonicum (11.8%), which are abundant species in meju, were also isolated frequently from rice straw. C. cladosporioides, F. asiaticum, and P. polonicum, which are abundant in the low temperature fermentation process of meju fermentation, were frequently isolated from rice straw incubated at 15°C and 25°C, whereas A. oryzae, E. repens, and E. chevalieri, which are abundant in the high temperature fermentation process of meju fermentation, were frequently isolated from rice straw incubated at 25°C and 35°C. This suggests that the mycobiota of rice straw has a large influence in the mycobiota of meju. The influence of fungi on the rice straw as feed and silage for livestock, and as plant pathogens for rice, are discussed as well.

No abstract