Arachidonic Acid and Its Metabolites as Differentiation Inducers for the Perfection of Wound Healing to Avoid Cancer and to Beat Cancer

The objective of this study is to explore the role of arachidonic acid and its metabolites in wound healing, cancer evolution, and cancer therapy. Cell Differentiation Agent-2 (CDA-2) was a promising hypomethylation agent approved by the Chinese FDA for the therapy of Myelo Dysplastic Syndrome (MDS). MDS is a disease attributable entirely to Cancer Stem Cells (CSCs). A drug effective for the therapy of MDS means that drug can also be effective for the eradication of CSCs. The active components of CDA- 2 are Differentiation Inducers (DIs) and Differentiation Helper Inducers (DHIs). DIs are chemicals capable of eliminating telomerase from abnormal Methylation Enzymes (MEs) found in human cancers and primitive stem cells such as Progenitor Stem Cells (PSCs) and Embryonic Stem Cells (ESCs). The major DIs of CDA-2 were organic acids without UV absorption. Without UV absorption as a guide, it was difficult to purify DIs of CDA-2 for identification. Thus, we pursued possible candidates to function as DIs. We were interested in Prosta Glandin E2 (PGE2) since it was linked to wound healing, which is a major biological function of PSCs and CSCs. CSC eradication has been a significant goal of our research. PGE2 was found in the previous study effective as a DI, which encouraged us to look into other PGs to function as DIs with better activity and stability, and less adverse side effects. PGJ2 and 16, 16-dimethylPGE2 were the two PGs, good as DIs for the development of CDA formulations. PGJ2 was active in the dosage ranges between 4 and 17 \(\mu\)M with a maximum to induce 86% NBT+cells at 17 \(\mu\)M. 16, 16-dimethylPGE2 was active in the dosage ranges between 10 and 32 \(\mu\)M with a maximum to induce 83% NBT+cells at 27 \(\mu\)M. DI activities of bicycloPGE2 and Arachidonic Acid (AA) were very close. Both were modestly active between 20 and 42 \(\mu\)M with a maximum of 42%-52% NBT+cells at 42 \(\mu\)M. Although AA is not very active as a DI, the strong synergistic potentiation of DI activity by pregnenolone can boost its usefulness as an effective DI. Our previous studies indicated that the DIs of CDA-2 were either in liposomal complexes with pregnenolone or in association with cell membrane fragments. AA may very well be a major DI of CDA-2. As a result, AA could be a useful surveillance DI for preventing cancer in healthy persons. This research also indicates that metabolites involved in wound healing are also involved in chemo-surveillance.