Abnormal cell morphology and cytotoxic effect are induced by 6-0-palmitol-ascorbate-2-0-phosphate, but not by ascorbic acid or hyperthermia alone

A new derivative of ascorbic acid (AsA), 6-0-palmitoyl-ascorbate 2-0-phosph ate (Asc2P6Pal) was developed to enhance the antitumor. activity of AsA. Wh en Ehrlich ascites tumor cells were treated with 50 mu M Asc2P6Pal at 37 de grees C or 42 degrees C for 1 h and then cultured for 20 h, most of cells e xhibited some morphological abnormalities, including exudation of intracell ular granules together with other contents on the cell membrane surface, re sulting in cell fragmentation. The abnormal features were further enhanced by a long term culture for 96 h and hear treatment at 42 degrees C. In cont rast, no abnormality was detected for untreated cells or cells tl eared wit h AsA (free acid) at 37 degrees C or 4.2 degrees C. Cells cultured for 96 h after the treatment sufferred from inhibition of DNA synthesis and prolife ration. This inhibition was markedly enhanced by combination with the hyper thermic treatment at 42 degrees C, but not for a short-term culture of 20 h after the treatment. No effects were seen upon similar treatment with AsA. The abnormal cells produced during culture for 20 h after the treatment we re evaluated to be viable, because they failed to be stained with trypan bl ue and retained most of the DNA synthesizing ability of Asc2P6Pal-untreated cells. However, they appeared and died after a continuous 76 h of culture (96 h).