Carcinostatic effects of diverse ascorbate derivatives in comparison with aliphatic chain moiety structures: Promotion by combined hyperthermia and reduced cytotoxicity to normal cells.
In this study, using human tongue squamous carcinoma cells (HSC-4) carcinostatic activity was compared for diverse L-ascorbic acid (Asc) derivatives, including the 'straight-C(16)-chain types', 6-O-palmitoyl-Asc (A6-P) and Asc-2-phosphate-6-O-palmitate sodium salt (APPS), as well as the 'branched-C(16)-chain types', Asc-2-phosphate-6-O-(2'-hexyl)decanoate (APHD), an isomer of APPS, and Asc-2,3,5,6-O-tetra-(2'-hexyl)decanoate (VCIP). The order of magnitude of the carcinostatic effects at 37°C was: APPS>A6-P = APHD>VCIP and at 42°C was APPS = A6-P>APHD>VCIP. Therefore, the two straight-C(16)-chain derivatives, APPS and A6-P, had a greater effect compared to the two branched-C(16)-chain Asc derivatives, which are considered to have more difficulty with 'orientation along cell-membrane-glycerolipid direction'. APPS-treated HCS-4 cells were observed for a decrease in cell number, cell shrinkage, pycnosis indicative of apoptosis and cell deformation. The order of cytotoxicity for the normal human dermal fibroblasts (OUMS-36) at 37°C was: A6-P (50% inhibitory concentration: 150-300 μM)>APHD (450-600 μM)>>Asc = APPS (800-1000 μM). Accordingly, APHD was more cytotoxic than APPS, since the straight-C(16)-chain type, which was eliminated after the enzymatic esterolysis of APPS, is metabolized via the 'fatty acid β-oxidation cycle' more efficiently in normal cells. Thus, APPS had a greater advantage over APHD, A6-P and VCIP in terms of carcinostatic effects at 37°C, carcinostasis promotion at 42°C and a decrease of cytotoxicity to normal cells. This observation suggests a marked potential for aliphatic chain-moiety structures as anticancer agents, due to their cancer-selective carcinostasis and combined efficacy with hyperthermia, without causing side effects.
Maybe Steve Brown or someone can interpret?
This "sounds" similar to what my alt. doc was interested in determining (by products) after observing that IV sodium ascorbate is a far superior immune stimulant to the ordinary commercial vitamin C injectibles that are derived from ascorbic acid (buffered ascorbic acid.)