海南哥纳香醇甲(GHM-10)对L1210细胞生物大分子合成的抑制作用

INHIBITORY EFFECT OF HOWIINOL A(GHM 10) ON THE SYNTHESIS OF BIOLOGICAL MACROMOLECULES IN L1210 CELLS

目的旨在研究ＧＨＭ１０对Ｌ１２１０细胞生物大分子合成的影响。用［３Ｈ］标记前体参入试验。结果表明，ＧＨＭ１０４～１２μｇ·ｍｌ－１作用６ｈ，可使Ｌ１２１０细胞的ＤＮＡ，ＲＮＡ及蛋白质的生物合成发生明显抑制，其中以抑制ＤＮＡ合成的作用最强。用［３Ｈ］ＴｄＲ参入曲线法、紫外吸收光谱移动法和荧光光谱移动法研究了ＧＨＭ１０抑制ＤＮＡ生物合成的机制。结果表明，ＧＨＭ１０６～８μｇ·ｍｌ－１作用Ｌ１２１０细胞１ｈ后，ＤＮＡ合成的抑制已不可逆。提示ＧＨＭ１０可能引起ＤＮＡ分子结构的损伤，但ＧＨＭ１０不能嵌入ＤＮＡ分子或直接破坏ＤＮＡ的结构。

Howiinol(GHM 10), a new compound isolated from Goniothalamus howii , had been shown to have marked anticancer activity both in vitro and in vivo . In the present study, the effect of GHM 10 on the biosynthesis of macromolecules in L1210 cells was investigated. By using labeled precursor incorporation assays, we found that the biosyntheses of DNA, RNA and protein in L1210 cells were inhibited markedly after the cells were pretreated with GHM 10 in 4～12 μg·ml -1 for 6 h and the inhibition of DNA synthesis was the most obvious one. We also used the methods of TdR incorporation curve, shift of UV absorption spectrum and shift of fluorescence spectrum to investigate the mechanism of inhibitory action of GHM 10 on DNA biosynthesis. The results showed that the inhibition of DNA synthesis already became irreversible after the L1210 cells were treated with GHM 10 in 6～8 μg·ml -1 for 1 h, indicating that GHM 10 may induce damage on DNA molecular structure. However, when calf thymus DNA was treated with GHM 10, the UV absorption spectrum and the fluorescence spectrum of the DNA were not changed significantly. It is suggested that GHM 10 was not able to intercalate into DNA molecules or to damage the structure of DNA directly.