Carcinogenesis Advance Access published online on February 23, 2006
Carcinogenesis, doi:10.1093/carcin/bgi348
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Biotechnology, Yonsei University, Seoul, Korea; Department of Food and Nutrition, Seoul National University, Seoul, Korea; Department of Dermatology, University of Wisconsin, Madison, WI, USA
* To whom correspondence should be addressed. Because of unsatisfactory treatment options for prostate cancer (CaP) there is a need to develop novel preventive approaches for this malignancy. One such strategy is through chemoprevention by the use of non toxic dietary substances and botanical products. We previously show that panduratin A isolated from the extract of Kaempferia pandurata (Zingiberaceae) is a strong inhibitor of cyclooxygenase-2 in RAW264.7 cells and induces apoptosis in HT-29 cells. In the present study, we provide evidence that panduratin A treatment to androgen-independent human CaP cells PC3 and DU145 result in a time and dose-dependent inhibition of cell growth with an IC50 of 13.5-14 µM and no to little effect on normal human prostate epithelial cells. To define the mechanism of these anti-proliferative effects of panduratin A, we determined its effect on critical molecular events known to regulate the cell cycle and the apoptotic machinery. Annexin V/propodium iodide staining provided the evidence for the induction of apoptosis which was further confirmed by the observation of cleavage of poly (ADP-ribose) polymerase and degradation of acinus. Panduratin A treatment to cells was found to result in inhibition of procaspases -9, -8, -6 and -3 with significant increase in the ratio of Bax to Bcl-2, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Panduratin A-mediated apoptosis was accompanied with up-regulation of Fas death receptor and TNF-related apoptosis-inducing ligand (TRAIL). Furhermore, cell cycle analysis using flow cytometry showed that panduratin A treatment of cells resulted in a G2/M arrest in a dose-dependent manner. The immunoblot analysis data revealed that in both cell lines panduratin A treatment resulted in a dose-dependent (i) induction of p21WAF1/Cip1 and p27Kip1, (ii) down regulation of cdk2, cdk4 and cdk6, and (iii) decrease in cyclin D1 and cyclin E. These findings suggest that panduratin A may be an effective chemopreventive or therapeutic agent against CaP.
Received July 26, 2005
Revised September 5, 2005
Accepted January 17, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Induction of apoptosis and cell cycle arrest by a chalcone panduratin A isolated from Kaempferia pandurata in androgen-independent human prostate cancer cells PC3 and DU145
Jung-Mi Yun 1,
Mee-Hyang Kweon 2,
Hoonjeong Kwon 3,
Jae-Kwan Hwang 4 *,
and
Hasan Mukhtar 2
2 Department of Dermatology, University of Wisconsin, Madison, WI, USA
3 Department of Food and Nutrition, Seoul National University, Seoul, Korea
4 Department of Biotechnology, Yonsei University, Seoul, Korea
Jae-Kwan Hwang, E-mail: jkhwang{at}yonsei.ac.kr
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Lu, L. Xia, H. Hua, and Y. Jing Acetyl-Keto-{beta}-Boswellic Acid Induces Apoptosis through a Death Receptor 5-Mediated Pathway in Prostate Cancer Cells Cancer Res., February 15, 2008; 68(4): 1180 - 1186. [Abstract] [Full Text] [PDF]
|
|