We recently identified HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of various retinoic acid responsive cancers. Lovastatin, a competitive inhibitor of HMG-CoA reductase, induced a retinoic acid-like differentiation response followed by extensive apoptosis in neuroblastoma cell lines at relatively low concentrations (<20 microM) of this agent. More recently, we demonstrated that acute myeloid leukemias but not acute lymphocytic leukemias also displayed increased sensitivity to lovastatin-induced apoptosis. In this study, we examined the ability of lovastatin to induce differentiation of acute myeloid leukemic cells and to evaluate the role differentiation may hold in the anti-leukemic properties of this agent. Increased expression of the leukocyte integrins CD11b and CD18 as well as down-regulation of the anti-apoptotic gene bcl-2 are associated with late stage differentiation of the myeloid lineage and retinoic acid induced maturation of acute myeloid leukemic cells. Lovastatin exposure induced increased expression of CD11b and CD18 markers similar to retinoic acid treatment. Following 24 hrs exposure to 20 microM lovastatin, all 7 acute myeloid leukemia cell lines tested showed a decrease in bcl-2 mRNA expression while only 1/5 acute lymphocytic leukemia cell lines showed a similar response. A role for bcl-2 in the apoptotic response of acute myeloid leukemia cells to lovastatin was demonstrated as exogenous constitutive expression of bcl-2 in the AML-5 cell line inhibited apoptosis in a time and dose dependent manner. Thus, lovastatin exposure of acute myeloid leukemia cells induced a differentiation response that may contribute to the therapeutic potential of this agent in the treatment of this disease.
Olive pomace (OP) is the main by‐product of olive oil extraction. After pit and skin removal, OP pulp has high concentrations of dietary fiber and phenolics with high antioxidant capacity. This study evaluated mice health benefits of drum‐dried pitted OP pulp obtained after first and second oil extraction. Fresh OP was steam blanched, then pits and skins separated in a pulper/finisher, and pulp drum‐dried and milled. OP was characterized by proximate analysis, total soluble phenolics (TSP), individual phenolics, and dietary fiber. Drum‐dried pitted OP from first and second extraction was formulated at 10% and 20% in a high fat mice diet. Low fat (5%) and high fat (18%) control diets were also used for comparison. First extraction OP had higher TSP than OP from second extraction. Hydroxytyrosol was the main phenolic in OP. Mice weight gain was lower for the four OP diets compared to high and low‐fat control diets. Fecal protein was high for all OP diets, indicating poor protein retention in mice, possibly by phenolics binding of protein and enzymes. Liver weight and adipose tissue were lower in mice consuming the four high fat OP diets compared to high fat control diet. Also, there was no effect on blood glucose by OP in diets. Mice gut microbiota analysis indicated that Actinobacteria decreased in the OP diets compared to the two control diets while Bacteroidetes increased, indicating a positive correlation with reduced body fat and weight. Drum‐dried pitted OP is a novel agricultural by‐product with its bioactive compounds having the potential to be incorporated in feeds and foods providing health benefits. Practical Application Drum‐dried pitted olive pomace can be produced from first or second olive oil extraction byproducts to be used as a shelf‐stable healthy food or feed supplement.
In the present work, the use of different freeze‐dried berry powders as stabilizers to avoid the melt‐down of frozen desserts was investigated. Samples were prepared using 3.5% freeze‐dried berry powder (strawberry, raspberry, blackberry, and blueberry) and compared with a control containing no berries. The addition of strawberry or raspberry powder completely prevented the melt‐down of the frozen desserts. These samples retained their original shapes once the ice crystals melted. Blackberry powder prevented the melting of the frozen desserts, but the foam structure collapsed and lost its original shape. The incorporation of blueberry powder did not prevent the melting of the frozen desserts. The blueberry samples showed phase separation with a fraction of clear serum. Practical applications Freeze‐dried strawberries and raspberries could be used to replace stabilizers in the production of “clean label” and nutritionally enhanced ice creams. Also, the production of frozen dairy desserts that do not melt at ambient temperature will allow the creation of complex structures using new technologies, such as 3D printing under ambient conditions.
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