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

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.