The goal of this research is to look at the role of arachidonic acid and its metabolites in wound healing, cancer progression, and cancer treatment. The Chinese FDA authorised Cell Differentiation Agent-2 (CDA-2) as a promising hypomethylation agent for the treatment of Myelo Dysplastic Syndrome (MDS). MDS is a condition caused only by cancer stem cells (CSCs). A medication that is effective in the treatment of MDS may also be effective in the treatment of CSCs. Differentiation Inducers (DIs) and Differentiation Helper Inducers (DHIs) are the active components of CDA-2 (DHIs). DIs are compounds that can remove telomerase from aberrant Methylation Enzymes (MEs) present in human malignancies and primitive stem cells such Progenitor Stem Cells (PSCs) and Embryonic Stem Cells (ESCs) (ESCs). CDA-2's main DIs were organic acids that did not absorb UV light. It proved challenging to purify CDA-2 DIs for identification without using UV absorbance as a guide. As a result, we looked for persons who could serve as DIs. Prosta Glandin E2 (PGE2) piqued our interest since it was associated to wound healing, which is a major biological function of PSCs and CSCs. Eradication of CSCs has been a major focus of our research. PGE2 was proven to be beneficial as a DI in a prior study, which prompted us to explore at other PGs that could work as DIs with improved activity and stability, as well as less negative side effects. The two PGs that worked well as DIs in the development of CDA formulations were PGJ2 and 16, 16-dimethylPGE2. PGJ2 was active at doses ranging from 4 to 17 M, with a high of 86 percent NBT+cells induction at 4 M. 17. M. 16, 16-dimethylPGE2 was active at doses ranging from 10 to 32 M, with a high of 83 percent NBT+cells being induced at 27 M. BicycloPGE2 and Arachidonic Acid (AA) had similar DI actions. Between 20 and 42 M, both were moderately active, with a maximum of 42 percent -52 percent NBT+cells at 42 M. Although AA is not very effective as a DI, pregnenolone's significant synergistic potentiation of DI action can increase its effectiveness as a DI. CDA-2 DIs were found in liposomal complexes with pregnenolone or in connection with cell membranes in prior research. bits of membrane CDA-2 could very possibly have AA as a major DI. As a result, AA could be an effective surveillance DI for cancer prevention in healthy people. This study also found that metabolites involved in wound healing play a role in chemo-surveillance.
Author (S) Details
Ming C. Liau
Department of Medicine, University of California, Irvine Medical Center, CA, USA.
Dr. Jai-Hyun Kim,
Department of Medicine, University of California, Irvine Medical Center, CA, USA.
John P. Fruehauf
Department of Medicine, University of California, Irvine Medical Center, CA, USA.
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