Skip Navigation



Carcinogenesis Advance Access published online on October 21, 2004
Carcinogenesis, doi:10.1093/carcin/bgh313
© 2004 by Oxford University Press
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/2/359    most recent
bgh313v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Lee, J.-Y.
Right arrow Articles by Surh, Y.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J.-Y.
Right arrow Articles by Surh, Y.-J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received June 6, 2004
Revised October 2, 2004
Accepted October 10, 2004

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Anti-tumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol type ginsenosides in mouse skin

Ji-Yoon Lee 1, Jun-Wan Shin 1, Kyung-Soo Chun 1, Kwang-Kyun Park 2, Won-Yoon Chung 2, Yung-Jue Bang 3, Jong-Hwan Sung 4, and Young-Joon Surh 5*

1 National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
2 College of Dentistry, Yonsei University, Seoul 120-742, South Korea
3 Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea
4 Ilhwa Co., Ltd., Guri-shi, Gyeonggi-do 471-711, South Korea
5 National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742, Korea; Ilhwa Co., Ltd., Guri-shi, Gyeonggi-do 471-711, South Korea

* To whom correspondence should be addressed.
Young-Joon Surh, E-mail: surh{at}plaza.snu.ac.kr


  Abstract

Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-{beta}-D-glucopyranosyl-20(S)-protopanaxadiol], an intestinal bacterial metabolite derived from protopanaxadiol type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation, and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. IH-901 pretreatment inhibited ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a female ICR mice. Topical application of IH-901 onto shaven backs of female ICR mice led to inhibition of TPA-induced expression of COX-2 and production of prostaglandin E2. The eukaryotic transcription factor NF-{kappa}B has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 attenuated TPA-induced epidermal NF-{kappa}B DNA binding in mouse skin which appeared to be mediated by blocking phosphorylation and subsequent degradation of I{kappa}B{alpha}. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-{kappa}B, its effects on activation of upstream signaling kinases were explored. IH-901 treatment mitigated the activation of ERK1/2 and Akt signaling. In another experiment, topically applied IH-901 suppressed the activity as well as expression of ODC in a dose-dependent fashion. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7,12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to its anti-tumor promoting effects on mouse skin carcinogenesis.

Keywords: Ginsenosides; IH-901; Mouse skin carcinogenesis; Cyclooxygenase-2; Anti-tumor promotion.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.