Fatty acids with conjugated double bonds such as Conjugated Linoleic Acid (CLA; cis-9, trans-11)) and Conjugated Linolenic Acids (CLNAs) such as �-eleostearic acid (ESA; Cis-9, trans-11, trans-13) and punicic acid (PA; cis-9, trans-11, cis-13) are reported with potent anti-cancer properties and this effect has been proven by in vitro and in vivo studies. The anti-cancer action of CLNAs is far more potent than that of CLA though only difference accounted to be the presence of an additional double bond at �13 position.
Interestingly, by numerous studies performed since 1999 revealed that these CLNAs would not survive within a cell (in vitro studies) or an animal (in vivo studies), hence rapidly converted in to CLA by a quick saturation of �13 double bond by an unknown mechanism and then incorporated into cellular lipids. Then the question arises on how the CLNAs could exhibit more potent anti-cancer properties than its metabolic end product, CLA. Thus, it reveals the fact that potent anti-cancer property of CLNAs are not mediated by themselves, but possibly though another metabolite.
On the other hand, retinoids, especially, the all-trans-retinoic acid reported with potent anti-cancer properties. Malignancies are associated with deficiencies of retinoids. Retinol saturase (RetSat) specifically reduces the C13-C14 double bond in all trans Retinol to form all trans 13-14 dihydroretinol, which will subsequently be converted to all-trans-13-14 dihydroretinal and then to all-trans -13-14 dihydroretinoic acid. RetSat reported to have a ubiquitous distribution in animal body. If the all-trans-Retinol can evade this saturation reaction by RetSat, it can be converted into its active form, all-trans -Retinoic acid (atRA). The all-trans-Retinoic acid is far superior ligand than all-trans -13-14 dihydroretinoic acid form for RAR and RXR receptors in nucleus. Cellular differentiation, cell proliferation and apoptosis, which play a key role in tumor growth suppression are efficiency regulated by all-trans -Retinoic acid signalling, but not by 13-14 dihydroretinoic acid. Thus RetSat activity may downgrade the potency of cellular level retinoid signalling.
Some researchers speculate that the hydrogenation or saturation of �13 double bond of CLNAs is mediated by RetSat. Thus, it can be hypothesized that CLNAs may compete for RetSat for quick hydrogenations of �13 double bond as fake substrate with its usual substrate all-trans-Retinol which, may be favoured by the RetSat activity. Then all-trans-Retinol may evade its conversion to all-trans-13-14 Dihydroretinol and further metabolized into active all-trans-Retinoic acid which could control numerous cellular processes helping the suppression of carcinogenesis.
For these reasons, it is hypothesized that the potent anti-cancer property of CLNAs may be mediated by this quick conversion of it to CLA, creating a competitive inhibition on hydrogenation of all-trans-Retinol by RetSat. As a result, abundance of all-trans-Retinoic acid would be increased at cellular level and it would induce key cellular mechanisms such as differentiation, apoptosis and controlling the proliferation of cells and thereby suppresses the occurrence of malignant cell growths.
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