abscisic-acid and Neoplasms

Abscisic acid (ABA) is an important phytohormone that regulates plant growth, development, dormancy and stress responses. Recently, it was discovered that ABA is produced by a wide range of animals including sponges (Axinella polypoides), hydroids (Eudendrium racemosum), human parasites (Toxoplasma gondii), and by various mammalian tissues and cells (leukocytes, pancreatic cells, and mesenchymal stem cells). ABA is a universal signaling molecule that stimulates diverse functions in animals through a signaling pathway that is remarkably similar to that used by plants; this pathway involves the sequential binding of ABA to a membrane receptor and the activation of ADP-ribose cyclase, which results in the overproduction of the intracellular cyclic ADP-ribose and an increase in intracellular Ca²⁺ concentrations. ABA stimulates the stress response (heat and light) in animal cells, immune responses in leukocytes, insulin release from pancreatic β cells, and the expansion of mesenchymal and colon stem cells. ABA also inhibits the growth and induces the differentiation of cancer cells. Unlike some drugs that act as cell killers, ABA, when functioning as a growth regulator, does not have significant toxic side effects on animal cells. Research indicated that ABA is an endogenous immune regulator in animals and has potential medicinal applications for several human diseases. This article summarizes recent advances involving the discovery, signaling pathways and functions of ABA in animals.

Topics: Abscisic Acid; Animals; Atherosclerosis; Diabetes Mellitus, Type 2; Granulocytes; Humans; Inflammatory Bowel Diseases; Islets of Langerhans; Microglia; Monocytes; Neoplasms; Phytotherapy; Plant Growth Regulators; Signal Transduction; Stem Cells

Angiogenesis is a complex biological process wherein novel capillary blood vessels mature from pre-existing vasculature for delivering tissues with oxygen and nutrients. Natural molecules that have anti-angiogenic activity and toxicity can raise the focus on using plant sources as essential therapeutic agent.. The current research was intended to estimate the probable anti-angiogenic activity of abscisic acid alone and in combination with prednisolone, a well-known angiostatic glucocorticoid.. two months old albino rats were used in this study. ABA and prednisolone stock solutions were prepared and added after embedding aortic rings in growth media. The ex vivo rat aorta ring assay (RAR) was applied to explore the anti-angiogenic effect of ABA. The in vivo chorioallantoic membrane assay (CAM) was applied to quantify the blood vessels inhibition zone by ABA effect. That zone was calculated as the mean inhibition region on eggs in mm ± SD.. Abscisic acid screened byex vivo and in vivo assays, revealed a significant dose-dependent blood vessels inhibition in comparison to the negative control with IC50= 7.5µg/ml and a synergism effect when combined with prednisolone.. The synergism activity of ABA with prednisolone can significantly inhibit blood vessels growth in RAR and CAM assays. These results shed the light on the potential clinic values of ABA, and prednisolone combination in angiogenesis-dependent tumors.

Topics: Abscisic Acid; Angiogenesis Inhibitors; Animals; Chorioallantoic Membrane; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic; Prednisolone; Rats

Cellular behaviors are governed by interaction networks among biomolecules, for example gene regulatory and signal transduction networks. An often used dynamic modeling framework for these networks, Boolean modeling, can obtain their attractors (which correspond to cell types and behaviors) and their trajectories from an initial state (e.g. a resting state) to the attractors, for example in response to an external signal. The existing methods however do not elucidate the causal relationships between distant nodes in the network.. In this work, we propose a simple logic framework, based on categorizing causal relationships as sufficient or necessary, as a complement to Boolean networks. We identify and explore the properties of complex subnetworks that are distillable into a single logic relationship. We also identify cyclic subnetworks that ensure the stabilization of the state of participating nodes regardless of the rest of the network. We identify the logic backbone of biomolecular networks, consisting of external signals, self-sustaining cyclic subnetworks (stable motifs), and output nodes. Furthermore, we use the logic framework to identify crucial nodes whose override can drive the system from one steady state to another. We apply these techniques to two biological networks: the epithelial-to-mesenchymal transition network corresponding to a developmental process exploited in tumor invasion, and the network of abscisic acid induced stomatal closure in plants. We find interesting subnetworks with logical implications in these networks. Using these subgraphs and motifs, we efficiently reduce both networks to succinct backbone structures.. The logic representation identifies the causal relationships between distant nodes and subnetworks. This knowledge can form the basis of network control or used in the reverse engineering of networks.

Topics: Abscisic Acid; Algorithms; Epithelial-Mesenchymal Transition; Gene Regulatory Networks; Humans; Models, Biological; Neoplasm Invasiveness; Neoplasms; Plant Stomata; Plants; Signal Transduction; Systems Biology