Retinoids Hamper Inflammation in Normal and Cancer Epithelial Cell Lines

Inflammation is considered one of major causes of cancer and hamper inflammation is possible target of chemotherapy and chemopreventive treatment. Retinoids have potential anti-inflammatory effects. We investigated the effects of the retinoid all-trans retinoic acid (RA) and the 6-OH-11-O-hydroxyphenantrene (IIF), a specific ligand of Retinoid XReceptor (RXR), on the normal keratinocyte cell line NCTC and on the neuroepithelioma cancer cell line SKNMC. IIF and RA treatment inhibited proliferation and viability in a time and dose dependent manner. Interestingly, IIF was significantly more effective than RA and reduced of 50% SKNMC cells after 24 h of treatment at the dose 30 μM. The effects are further evident in cancer cells than normal cells where retinoids reduce slightly the viability. We stimulated inflammation with LPS and TNFα in normal and cancer cells and we observed the effects of IIF on several catechins involved in inflammation. A reduction of TNFα, IL2 expression and IL6 production after treatment with IIF in SKNMC cells was reported. Moreover, IIF reduced IL18, IL15 and IFNγ expression in inflammatory NCTC cells. Finally, inflammation induction increased while IIF treatment reduced matrix metalloproteinase-2 and -9 activity, two proteins that are involved in cell invasion and metastasis. In conclusion, we suggest that retinoids as IIF could be used to overcome inflammation in human carcinoma and it may be a powerful tool in the development of cancer therapies.