Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells.
The in vitro cytotoxicities of the ethanol extract of Andrographis paniculata (APE) and its main diterpenoid components were evaluated in various cancer cells. APE was found to be significantly growth inhibitory to human acute myeloid leukemic HL-60 cells with an IC (50) value of 14.01 microg/mL after 24 h of treatment. Among the three main diterpenoids in A. paniculata, andrographolide exhibited the highest degree of cytotoxicity followed by deoxyandrographolide while neoandrographolide was the least effective. Laser confocal microscopy and gel electrophoresis studies revealed chromosomal DNA fragmentations suggesting the occurrence of apoptosis. An increase of G (0)/G (1) phase cells from 51.88 % to 78.69 % was noted after andrographolide treatment for 36 h. The G (0)/G (1) phase arrest and apoptosis were associated with disappearance of mitochondrial cytochrome c and increased expression of Bax but decreased expression of Bcl-2 proteins in the inhibited cells. Although the order of all these events has not been determined, it is concluded that APE and andrographolide induce cell cycle arrest and affect an intrinsic mitochondria-dependent pathway of apoptosis by regulating the expression of some pro-apoptotic markers in HL-60 cells.
Cheung
Hon-Yeung
HY
Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China. bhhonyun@cityu.edu.hk
Cheung
Sau-Ha
SH
Li
Jieliang
J
Cheung
Chui-Shan
CS
Lai
Wai-Ping
WP
Fong
Wang-Fun
WF
Leung
Fo-Man
FM
D035685:Andrographis / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D015394:Molecular Structure; D008517:Phytotherapy
D004224:Diterpenes; C030419:andrographolide