Kageyama K, Onoyama Y, Kimura M, Yamazaki H, Miwa N
Radioisotope Centre, Osaka City University Medical School, Japan.
Int J Hyperthermia. 1991 Jan-Feb;7(1):85-91. doi: 10.3109/02656739109004979.
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.
研究了单酰基或二酰基抗坏血酸盐与热处理的联合抗肿瘤作用，并与母体化合物L-抗坏血酸（AsA）进行了比较。在37℃时，75μM的6-O-棕榈酰（6P）和6-O-硬脂酰（6S）抗坏血酸盐显著抑制艾氏腹水癌细胞中的DNA合成。42℃热疗1小时可增强这种抑制作用。相比之下，即使在高达100μM的浓度下，AsA或2,6-O-二棕榈酰抗坏血酸盐（DP）在37℃或42℃时也不会产生抑制作用。结果表明，抑制作用不是由脂肪酸部分本身引起的；更有可能是由单酰化AsA的疏水性和亲水性平衡引起的，而二酰化或完整的AsA没有这种特性。肿瘤细胞热疗期间暴露于6P引起的DNA合成抑制大于热疗前或热疗后。如从薄层色谱图获得的放射曲线所示，6P或6S，但不是AsA或DP，从用[14C]油酸标记的细胞中释放出磷脂，如磷脂酰胆碱和磷脂酰乙醇胺。细胞膜的损伤似乎与单酰化AsA引起的DNA合成抑制有关，单酰化AsA具有表面活性。
