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Carcinogenesis Advance Access originally published online on October 17, 2007
Carcinogenesis 2007 28(12):2521-2529; doi:10.1093/carcin/bgm137
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells

Feng-Min Lin1, Li-Ru Chen1, En-Hau Lin1,2, Ferng-Chun Ke2, Hsin-Yi Chen1, Meng-Jen Tsai2 and Pei-Wen Hsiao1,*

1 Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Road, Sec. 2, Nan-Kang, Taipei 11529, Taiwan
2 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan

* To whom correspondence should be addressed. Tel: +886 2 2651 5747; Fax: +886 2 2785 9360; Email: pwhsiao{at}gate.sinica.edu.tw

Chronic inflammation can augment tumor development in various types of cancers, including prostate cancer (PCa). Reduction of inflammation is therefore an important anticancer therapeutic opportunity. Here, we report four anti-proliferative phytocompounds in Wedelia chinensis, an oriental herbal medicine, identified through their ability to modulate the androgen receptor (AR) activation of transcription from prostate-specific antigen promoter in PCa cells. The 50% inhibition concentration values of indole-3-carboxylaldehyde, wedelolactone, luteolin and apigenin, were 34.9, 0.2, 2.4 and 9.8 µM, respectively. A formula that combined the phytocompounds in the same proportions as in the herbal extract decreased the dosage of each compound required to achieve maximal AR inhibition. In correlation with the AR suppression effect, these active compounds specifically inhibited the growth of AR-dependent PCa cells and as a combination formula they also synergistically suppressed growth in AR-dependent PCa cells. Our study has identified synergistic effects of active compounds in W. chinensis and demonstrated their potential in PCa prevention and therapy. The paradigm of multiple activities and synergism is a useful framework to investigate the therapeutic effects of whole extracts from assorted medicinal plant species.

Abbreviations: Api, apigenin; AR, androgen receptor; CHCl3, chloroform; CI, combination index; DIM, diindolylmethane; EtOAc, ethyl acetate; EtOH, ethanol; H2O-Sub, H2O subfraction; HPLC, high-performance liquid chromatography; IC50, 50% inhibition concentration; ICA, indole-3-carboxylaldehyde; I3C, indole-3-carbinol; Lut, luteolin; PCa, prostate cancer; PSA, prostate-specific antigen; PSA-Luc, prostate-specific antigen-luciferase; Wed, wedelolactone

Received March 23, 2007; revised June 6, 2007; accepted June 6, 2007.


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