[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 [3H] 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 micrograms.ml-1 for 6 h and the inhibition of DNA synthesis was the most obvious one. We also used the methods of [3H]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 micrograms.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.
He
J
J
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050.
Xu
C
C
D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011753:Pyrones / Q000302:isolation & purification / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D004365:Drugs, Chinese Herbal; D009363:Neoplasm Proteins; D011753:Pyrones; D012334:RNA, Neoplasm; C426486:howiinol A