Enhanced inhibition of DNA synthesis and release of membrane phospholipids in tumour cells treated with a combination of acylated ascorbate and hyperthermia

Abstract

Combined antitumour effects of mono- or diacyl ascorbates and heat treatment were studied in comparison with the parent compound, L-ascorbic acid (AsA). At 37 degrees C, 75 microM 6-O-palmitoyl (6P) and 6-O-stearoyl (6S) ascorbates appreciably inhibited DNA synthesis in Ehrlich ascites tumour cells. Hyperthermia at 42 degrees C for 1 h increased the inhibition. In contrast, AsA or 2,6-O-dipalmitoyl ascorbate (DP), even at concentrations as high as 100 microM, caused no inhibition at 37 degrees C or 42 degrees C. The results suggest that the inhibitory action is not caused by the fatty acid moiety itself; it is more likely to be caused by the balance in the hydrophobicity and hydrophilicity of the monoacylated AsA, a property not found in diacylated or intact AsA. Inhibition of DNA synthesis caused by exposure to 6P during hyperthermia of tumour cells was greater than before or after hyperthermia. 6P or 6S, but not AsA or DP, released phospholipids such as phosphatidylcholine and phosphatidylethanolamine from cells labelled with [14C]oleic acid, as shown by radiocurves taken from thin-layer chromatograms. Damage of the cell membrane seemed to be involved in the inhibition of DNA synthesis caused by monoacylated AsA, which is surface-active.

Anticancer effects of 6-o-palmitoyl-ascorbate combined with a capacitive-resistive electric transfer hyperthermic apparatus as compared with ascorbate in relation to ascorbyl radical generation

“…4). We previously reported that anti-cell proliferation activity of diverse monoacylated Asc was not caused by the fatty acid moiety itself; it is more likely to be caused by the balance in the hydrophobicity and hydrophilicity of the monoacylated Asc (Kageyama et al 1991). Results of the present study might be explained by the continuous breakdown of cell membrane by Asc6Palm owing to an enhanced intracellular permeability by ester-linked palmitate.…”

Scavenging and antioxidant properties of compound derived from chlorogenic acid in South-China honeysuckle

“…L-ascorbyl palmitate, composed by hydrophilic ascorbyl moiety and hydrophobic palmitate moiety, has been widely used as surfactant and liposoluble antioxidant (Nippo, 1991). When compared with Lascorbyl acid, it has the remarkable enhancement of antioxidant and antitumor activities (Kageyama, Onoyama, & Kimura, 1991). Ascorbyl phosphate ester can be hydrolyzed by the phosphorylase in mammals.…”

The antitumor activities of the structurally-similar two-species aromatics Tonalide and Pearlide and the enhancement of their effects by hyperthermia

“…Synergistic enhancement of the effects of Tonalide and Pearlide was observed by applying them in combination with hyperthermia, which is known to inhibit the growth (12)(13)(14) and DNA synthesis (15)(16)(17) of tumor cells. Carcinostatic effect was evaluated as a decrease in mitochondrial dehydrogenase activity reflecting the survival rate of cells as measured by the WST-1 assay (18,19), and also as a decrease in viable cells according to the degree of staining determined by the trypan blue dyeexclusion assay (20,21).…”

“…Examination for carcinostatic effects in cultured tumor cells. Examination was essentially conducted as previously described (5,17). In brief, cells were suspended in culture medium at a density of 2x10 5 or 2x10 4 cells/ml for a 20-or 72-h culture test, respectively.…”