African Journal of
Pharmacy and Pharmacology

  • Abbreviation: Afr. J. Pharm. Pharmacol.
  • Language: English
  • ISSN: 1996-0816
  • DOI: 10.5897/AJPP
  • Start Year: 2007
  • Published Articles: 2250

Full Length Research Paper

Andrographolide induces cell cycle arrest and apoptosis in PC-3 prostate cancer cells

Hui Chyn Wong1, Sreenivasa Rao Sagineedu1, Nordin Haji Lajis1, Seng Cheong Loke2 and Johnson Stanslas1,3*
1Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia 2Institute of Gerontology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia 3Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Email: [email protected], [email protected]

  •  Accepted: 09 February 2011
  •  Published: 28 February 2011

Abstract

Andrographolide (AGP), the major phytoconstituent isolated from Andrographis paniculata was found to exhibit growth inhibition and cytotoxicity against the hormone-independent (PC-3 and DU-145) and hormone-dependent (LNCaP) prostate cancer cell lines via the microculture tetrazolium (MTT) assay. Due to its greater cytotoxic potency and selectivity towards PC-3 cells, flow cytometry was used to analyze the cell cycle distribution of control and treated PC-3 cells whereas Annexin V-FITC/PI flow cytometry analysis was carried out to confirm apoptosis induced by AGP in PC-3 cells. Cell cycle and apoptotic regulatory proteins were determined by western blot analysis. AGP was found to induce G2/M cell cycle arrest which led to predominantly apoptotic mode of cell death. Mechanistically, AGP was found to downregulate CDK1 without affecting the levels of CDK4 and cyclin D1. Induction of apoptosis was associated with an increase in activation and expression of caspase 8 which then is believed to have induced cleavage of Bid into tBid. In addition, activation and enhancement of executioner caspase 9 and Bax proteins without affecting Bcl-2 protein levels were observed.

 

Key words: Andrographolide, prostate cancer, cell cycle, cyclin-dependent kinases, apoptosis, caspase 8, caspase 9, Bcl-2 family.