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Carcinogenesis Advance Access published online on October 17, 2007
Carcinogenesis, 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, Taipei, Taiwan
2 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan

* Author for all correspondence: Dr. Pei-Wen Hsiao, Address: Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Road, Sec. 2, Nan-Kang, Taipei 115, Taiwan. Phone: +2-2651-5747. Fax: +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 anti-cancer 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 (PSA) promoter in PCa cells. The IC50 values of indole-3-carboxylaldehyde (ICA), wedelolactone (Wed), luteolin (Lut), and apigenin (Api), 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 Wedelia 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.

Key Words: Prostate cancer • androgen • chemoprevention • anti-inflammation • Wedelia chinensis • bioactivity-guided fractionation • synergism

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


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