2 research outputs found
Stem Cells and Extracellular Vesicles: Biological Regulators of Physiology and Disease
This is an extraordinary time in cell biology with evolving data pushing a reconsideration of the stability of cell systems and the regulatory mechanisms underlying cell phenotypes, especially the functional cell phenotypes. In this chapter, we will explore new insights into stem cell and extracellular vesicle biology with a focus on the role of extracellular vesicles in normal stem cell physiology as well as in various disease states. Extracellular vesicles (EVs) are being recognized as influential mediators of cellular function and potential experimental therapeutic strategies for a number of disorders outlined in this review. An evolving paradigm indicates a dynamic flux of EV populations within these disease states. We conclude our discussion of EV by extending our knowledge of robust EV biology toward disease detection and prognostication. Characterizing the biophysical and functional changes of vesicles amid disease progression or regression enables investigators to merge this information flux with existing deep learning computational and statistical techniques—allowing knowledge to be abstracted from large data sets profiling the biology of EVs within various disease states. Understanding how EV population shifts represent disease regression or progression creates paramount potential for EVs as salient and clinically relevant diagnostic and prognosticating tools
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Inhibition of BCL2 expression and activity increases H460 sensitivity to the growth inhibitory effects of polyphenon E
The anti-cancer properties of the green tea-derived mixture Polyphenon E (Poly E) have been demonstrated in a variety of cell culture and animal models. We recently discovered that the H460 lung cancer cell line is markedly resistant to the growth inhibitory effects of Poly E compared with SW480 colon and Flo-1 esophageal cancer cells. We investigated the mechanism of H460 resistance by comparing gene expression profiles of Poly E-sensitive and -resistant cells. Unsupervised hierarchical clustering revealed that Poly E-sensitive cells clustered separately from Poly E-resistant cells, and 6,242 genes were differentially expressed between the two groups at the 0.01 level of significance. We discovered that BCL2 gene and protein expression were significantly higher in H460 cells compared with SW480 and Flo-1 cells (10.60-fold higher gene expression; P < 0.0001). Inhibition of BCL2 expression and activity, using siRNA and the small molecule inhibitor HA14-1 respectively, restored sensitivity to Poly E and induced BCL2-related apoptosis by decreasing mitochondrial membrane potential and inducing PARP cleavage. Our results suggest that increased BCL2 expression may contribute to H460 resistance to the growth inhibitory effects of Poly E. If validated in additional laboratory and clinical models, BCL2 could ultimately be used as a marker of Poly E resistance