Effects of albaconol from the basidiomycete Albatrellus confluens on DNA topoisomerase II-mediated DNA cleavage and relaxation.
The effect of albaconol on the growth of human tumor cell, DNA topoisomerase (topo)-mediated DNA cleavage and direct DNA breakage was investigated. Albaconol inhibited significantly the growth of the human tumor cell lines K562, A549, BGC-823 and Bcap-37, the IC5s values were 7.99 +/- 0.4, 3.17 +/- 0.89, 4.18 +/- 0.14 and 7.45 +/- 2.5 microM, respectively. Albaconol stabilized and increased the topo 11-mediated DNA cleavable complex and inhibited the religation activity of topo II in a dose-dependent manner, but it failed to affect the activity of topo I. Albaconol directly broke pBR322 DNA at high concentrations, but there was no effect on the macromolecule of K562 cells. These results strongly suggest that albaconol targeted specifically to DNA topo II and that this is one of the mechanisms of its antitumor action; the direct action of albaconol on DNA may partly contribute to its anti-tumor activity at high concentrations.
Qing
Chen
C
Yunnan Key Laboratory of Pharmacology for Natural Products Research, Kunming Medical College, Kunming 650-204, P.R. China.
Liu
Ming-Hua
MH
Yangl
Wei-Min
WM
Zhang
Yan-li
YL
Wang
Lei
L
Liu
Ji-Kai
JK
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001487:Basidiomycota; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D010636:Phenols; D010936:Plant Extracts; D059005:Topoisomerase II Inhibitors; C478999:albaconol; D004250:DNA Topoisomerases, Type II