Cytoprotective effects of the lipoidic‐liquiform pro‐vitamin C tetra‐isopalmitoyl‐ascorbate (VC‐IP) against ultraviolet‐A ray‐induced injuries in human skin cells together with collagen retention, MMP inhibition and p53 gene repression

Abstract

Irradiation with ultraviolet-A (UVA) ray at doses of 20-100 J/cm(2) diminished the cell viability of human keratinocytes HaCaT and human melanoma cells HMV-II, both of which were protected by pre-irradiational administration with the ascorbic acid (Asc) derivative, VC-IP (2,3,5,6-O-tetra-2'-hexyldecanoyl-L-ascorbic acid; vitamin C-isopalmityl tetraester), which is the first lipoidic-liquiform pro-vitamin C by itself that is materialized by esterization of all four intramolecular hydroxyl groups of an Asc molecule with branched chain fatty groups, resulting in molecular fluidity higher than that of the corresponding straight chains. Irradiation with UVA to HaCaT keratinocytes was shown to cause the formation of 8-hydroxydeoxyguanosine (8-OHdG), translocation of phosphatidylserine in the inner layer into the outer layer of cell membrane, and lowering of a mitochondrial membrane potential, all of which were repressed by pre-irradiational administration with VC-IP. Expression of p53 gene, another hallmark of UV-induced DNA damages, was promoted by UVA irradiation to the keratinocytes but also repressed by VC-IP. Administration with VC-IP of 10-50 microM to human fibroblasts NHDF achieved the enhancement of collagen synthesis, repression of matrix metalloprotease-2/9 activity, and increasing of intracellular Asc contents more markedly than that with Asc itself of the same concentrations. Thus UVA-induced diverse harmful effects could be prevented by VC-IP, which was suggested to ensue intrinsically from the persistent enrichment of intracellular Asc, through esterolytic conversion of VC-IP to a free-form Asc molecule, resulting in relief to UVA-caused oxidative stress.

Protective effects of vitamin C derivatives on skin atrophy caused by Sod1 deficiency

“…Matsuda et al (2008) reported that VCP-IS-2Na inhibited melanogenesis in human melanoma cells and epidermal melanocytes. In addition, Xiao et al (2009) reported that 2,3,5,6-O-tetra-2'-hexyldecanoyl L-ascorbic acid in a liquid form showed cytoprotective effects against UV-A ray-induced injuries in human skin cells. Saitoh et al (2009) reported that a fucoidan-vitamin C complex suppressed tumor invasion through the basement membrane via decreased oxidative stress and metalloproteinase activity in human fibrosarcoma cells.…”

MiR-21: an environmental driver of malignant melanoma?

“…Notably, miR-21 expression has been associated with exposure to diesel exhaust linked to increased plasma levels of 8-hydroxy-deoxyguanosine (8-OHdG) [ 238 ]. 8-OHdG is induced in DNA by oxidative stress and UV irradiation [ 239 ]. Indeed, melanoma patients with low expression of nuclear 8-OHdG have significantly longer survival times compared to those with high expression [ 240 ].…”

Differential modulation of stress-inflammation responses by plant polyphenols in cultured normal human keratinocytes and immortalized HaCaT cells

“…Keratinocytes appear to be not only primary sensors of stressful conditions but also major players of the extremely complex immune response in the skin conducting an orchestrated recruitment and functions of other immune cells involved in a stress-inflammation skin reaction [4]. Therefore cultured keratinocytes have become a prototype model for screening of anti-inflammatory, photo-protective, and cancer preventive substances for topical application [5][6][7][8].…”