Anti-proliferation, cell cycle arrest and apoptosis induced by a natural xanthone from Gentianopsis paludosa Ma, in human promyelocytic leukemia cell line HL-60 cells.
1-hydroxy-3,7,8-trimethoxyxanthone (xanthone 1) was isolated from Gentianopsis paludosa Ma and identified by MS and NMR in our laboratory. In this study, the results showed that xanthone 1 is a potent inducer of anti-proliferation and apoptosis in HL-60 cells. When the cells treated with lower concentrations of xanthone 1 (12.4-74.4microM), significant proliferation inhibition was detected by cell viability assay and morphological analyses, and conspicuous G1 and G2/M cell cycle arrest were observed by flow cytometric (FCM) analysis. However, when the cells treated with higher doses of xanthone 1 (82.7-330.8microM), significant apoptosis was observed by double sequential AO/EB staining, DNA fragmentation assay and FCM analysis. In addition, conspicuous DNA damage was detected by comet assay. In short, all the results showed that xanthone 1 had a significant cytotoxic effect and could induce proliferation inhibition and apoptosis in HL-60 cells in a time- and dose-dependent manner. It was possible that xanthone 1 could induce DNA damage in HL-60 cells, which resulted in G1 phase arrest at the lower concentrations and G2/M phase arrest at the higher concentrations, thus inhibiting the cell proliferation, and irreparable DNA damage at the higher concentrations might be responsible for the occurrence of apoptosis.
Ding
Lan
L
College of Life Sciences, Northwest Normal University, No. 967 Anning East Road, Lanzhou 730070, PR China. dinglan@nwnu.edu.cn
Liu
Bo
B
Qi
Lin-Lin
LL
Zhou
Qi-Yin
QY
Hou
Qian
Q
Li
Juan
J
Zhang
Qiong
Q