Planta Med 2005; 71(12): 1106-1111
DOI: 10.1055/s-2005-873128
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Andrographolide Isolated from Andrographis paniculata Induces Cell Cycle Arrest and Mitochondrial-Mediated Apoptosis in Human Leukemic HL-60 Cells

Hon-Yeung Cheung1 , 2 , Sau-Ha Cheung2 , Jieliang Li1 , Chui-Shan Cheung1 , Wai-Ping Lai2 , Wang-Fun Fong1 , Fo-Man Leung1
  • 1Department of Biology & Chemistry, City University of Hong Kong, Hong Kong SAR, China
  • 2Pharmaceutical & Chemical Technology Center Ltd., City University of Hong Kong, Hong Kong SAR, China
Further Information

Publication History

Received: November 8, 2004

Accepted: June 24, 2005

Publication Date:
25 October 2005 (online)

Abstract

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 IC50 value of 14.01 μg/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 G0/G1 phase cells from 51.88 % to 78.69 % was noted after andrographolide treatment for 36 h. The G0/G1 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.

Abbreviations

APE:extract of Andrographis paniculata

DSAM:deoxyandrographolide succinic acid monoester

HIV:human immunodeficiency virus

MTT:3-[4,5-dimethylthiazol-2-yl]-3,5-diphenyl-tetrazolium bromide

AO/EB:acridine orange/ethidium bromide

PBS:phosphate buffer saline

FACS:fluorescence-activated Cell Sorting system

PI:propidium iodide

SDS-PAGE:sodium dodecyl polyacrylamide gel electrophoresis

ECL:enhance dchemiluminescence

References

Dr H.-Y. Cheung

Department of Biology & Chemistry

City University of Hong Kong

83 Tat Chee Avenue

Kowloon

Hong Kong SAR

People’s Republic of China

Phone: +852-2788-7746

Fax: +852-2788-7406

Email: bhhonyun@cityu.edu.hk