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Growth Inhibitory Effects of Unsaturated Linoleinic Acid with Conjugated Double Bonds for Cancer Prevention

Rakesh Sharma, Yashwant Pathak

Abstract


The unsaturated fatty acids are positional and geometrical isomers with many conjugated double bonds. These conjugated unsaturated fatty acids may show potential growth inhibitory effects for cancer prevention. The conjugated fatty acids converted from unconjugated n-3 PUFAs may have high tumor -inhibiting activity than unconjugated n-3 PUFAs themselves. The combination of radiation with cEPA fatty acids act as selective inhibitor of mammalian pols and human topos by expression of pols b, d and e in cancer cell replication to induce radio sensitization to enhance susceptibility to apoptosis. The conjugated PUFAs cEPA and cDHA were prepared by alkaline treatment. The purified calf pol a, rat pol b, human pol g, human pols d, e and l had high activity in the inhibition assay. Inhibition by conjugated and non-conjugated compounds was dose-dependent, with 50% inhibition of pol a enzyme. The inhibitory effect of cEPA was stronger on both pols and topos than that of cDHA effect. The magnitude of inhibition by EPA and cEPA was in the order of pol γ > pol a. The cEPA reduced the DNA replication in mitochondria and nucleus. The HCT116 cells showed the ability to repair the damaged DNA containing DSBs caused by X-ray irradiation. The cEPA prevented the repair of damaged DNA by inhibiting the activity of pols b, d, e, and l, associated with nuclear DNA repair. The combined cEPA and radiation showed significantly lower expression of pols b, d and e in cells than cEPA treatment alone. The expression level of pol e  to catalyze DNA replication and repair, showed highest reduction in mRNA. These data indicated that the post-irradiation process enhanced the susceptibility to apoptosis while cEPA induced radio sensitization in cancer cells. The preliminary investigation into the effects of a combined radiation with cEPA, offers a selective inhibitor of mammalian pols and human topos. The capacity of cEPA enhanced radio sensitivity of HCT116 cells, reduced expression of DNA repair -related pols such as pols b, d and e enzymes and inactive repair of X-ray irradiation damaged DNA, DSBs in HCT116 cells. Preliminary observations and review put evidence of combined cEPA and radiation treatment induced potential anti-cancer effects on cancer cells such as induction of cancer cell death and apoptosis in favor of clinical trials on combined cEPA and radiation treatment. The combining selective inhibitors of DNA repair-related pols, such as cEPA, with X-ray irradiation might have clinical potential as a cancer treatment strategy.

 


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