Effects of antitumor compounds isolated from Pteris semipinnata L on DNA topoisomerases and cell cycle of HL-60 cells.
OBJECTIVE
To study the effect of the antitumor compounds 5F, 6F, and A from Pteris semipinnata L on the activities of DNA topoisomerases and cell cycle of HL-60 cells, and the synergism of compound 6F in combination with genistein in vitro.


METHODS
DNA topoisomerases were isolated from HL-60 cell lines, and supercoiled pBR322 DNA was used as substrate to determine the activities of DNA topoisomerase I and II. Cell cycle was analyzed by flow cytometry (FCM). Cytotoxicity assay was tested by MTT method.


RESULTS
Compounds 5F, 6F, and A inhibited the activities of DNA topoisomerase I and II. After exposure of the cells to compound 6F, an increase in cells in the S and G2/M phases and a decrease in cells in the G0/G1 phase of the cell cycle were observed. At low concentrations (57.8 and 115.6 nmol.L-1), compound 6F enhanced the cytotoxicity against HL-60 cell line in combination with genistein, q values were > 1.15. The enhancement times of 57.8 and 115.6 nmol.L-1 of 6F by genistein were 2.60 and 4.65, respectively.


CONCLUSIONS
Compounds 5F, 6F, and A inhibited the activities of DNA topoisomerases of HL-60 cells. Compound 6F increased the number of cells in S and G2/M phases, decreased the population of G0/G1 phase cells, and enhanced the cytotoxicity of genistein, which had synergism with 6F in antitumor action.
Li
J H
JH
Institute of Medical Biochemistry, Guangdong Medical College, Zhanjiang, China. gdmcsh@gdmc.edu.cn
He
C W
CW
Liang
N C
NC
Mo
L E
LE
Zhang
X
X
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D018922:HL-60 Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D019833:Genistein; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II