Carcinostatic effects of diverse ascorbate derivatives in comparison with aliphatic chain moiety structures: Promotion by combined hyperthermia and reduced cytotoxicity to normal cells
- Authors:
- Published online on: February 22, 2012 https://doi.org/10.3892/ol.2012.615
- Pages: 1042-1046
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Abstract
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-C16-chain types’, 6-O-palmitoyl-Asc (A6-P) and Asc-2-phosphate-6-O-palmitate sodium salt (APPS), as well as the ‘branched-C16-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‑C16‑chain derivatives, APPS and A6-P, had a greater effect compared to the two branched-C16-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‑C16‑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.
