POTENTIATION OF CYTOTOXICITY OF MITOMYCIN-C BY A POLYACETYLENIC ALCOHOL, PANAXYTRIOL

Polyacetylenic alcohol, panaxytriol, which was isolated from Panax ginseng C. A. Meyer, has antiproliferative activity against several kinds of tumor cells. In this paper, die effect of panaxytriol on the cytotoxicity of mitomycin C (MMC) against a human gastric carcinoma cell line, MK-1, was investigated. The combination of a subthreshold concentration of MMC and panaxytriol produced a significant cytotoxic effect, which indicates that the effects of panaxytriol and MMC are synergistic. A synergistic effect was observed when MK-1 cells were treated with the mixture of MMC and panaxytriol or treated with MMC followed by panaxytriol. In contrast, when MK-1 cells were exposed to panaxytriol and then to MMC, only an additive effect was induced. With the aim of finding a possible mechanism, the effect of panaxytriol on the accumulation of MMC into the MK-1 cells was examined. Cellular concentrations of MMC were measured by high-performance liquid chromatography (HPLC). When MK-1 cells were treated with a mixture of panaxytriol and MMC or first with MMC and then with panaxytriol, the cellular level of MMC was significantly higher than that in MK-1 cells treated with MMC alone, but no significantly increased accumulation was found when MK-1 cells were treated with panaxytriol followed by MMC. These results suggest that synergistic effects of panaxytriol and MMC may be induced by acceleration of the effect of MMC on cellular accumulation by panaxytriol. In addition, they suggest that the enhanced accumulation of MMC in MK-1 cells treated with panaxytriol can probably be attributed to the decreased fluidity of the cell membrane caused by panaxytriol.