16497706

pubmed:Citation

7

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 have shown previously 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 microM 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/propidium 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:Bcl-2, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Panduratin A-mediated apoptosis was accompanied with upregulation of Fas death receptor and TNF-related apoptosis-inducing ligand (TRAIL). Furthermore, 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) downregulation of cdks 2, 4 and 6 and (iii) decrease in cyclins D1 and E. These findings suggest that panduratin A may be an effective chemopreventive or therapeutic agent against CaP.

eng

IM

MEDLINE

0143-3334

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NLM

1454-64

pubmed-meshheading:16497706-Adenocarcinoma, pubmed-meshheading:16497706-Androgens, pubmed-meshheading:16497706-Apoptosis, pubmed-meshheading:16497706-Apoptosis Regulatory Proteins, pubmed-meshheading:16497706-Blotting, Western, pubmed-meshheading:16497706-Caspases, pubmed-meshheading:16497706-Cell Cycle, pubmed-meshheading:16497706-Cell Line, Tumor, pubmed-meshheading:16497706-Chalcones, pubmed-meshheading:16497706-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:16497706-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:16497706-Cyclin-Dependent Kinases, pubmed-meshheading:16497706-Cyclins, pubmed-meshheading:16497706-Dose-Response Relationship, Drug, pubmed-meshheading:16497706-Flow Cytometry, pubmed-meshheading:16497706-Humans, pubmed-meshheading:16497706-Inhibitory Concentration 50, pubmed-meshheading:16497706-Male, pubmed-meshheading:16497706-Membrane Glycoproteins, pubmed-meshheading:16497706-Phytotherapy, pubmed-meshheading:16497706-Plant Extracts, pubmed-meshheading:16497706-Prostatic Neoplasms, pubmed-meshheading:16497706-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16497706-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:16497706-Tumor Necrosis Factor-alpha, pubmed-meshheading:16497706-Zingiberaceae, pubmed-meshheading:16497706-bcl-2-Associated X Protein, pubmed-meshheading:16497706-bcl-Associated Death Protein

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.

Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural