Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging

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Title:	Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging
Authors:	Yeh, CT (Yeh, Chi-Tai) Rao, YK (Rao, Yerra Koteswara) Ye, M (Ye, Min) Wu, WS (Wu, Wen-Shi) Chang, TC (Chang, Tung-Chen) Wang, LS (Wang, Liang-Shun) Wu, CH (Wu, Chih-Hsiung) Wu, ATH (Wu, Alexander T.H.) Tzeng, YM (Tzeng, Yew-Min)
Contributors:	Dept Hort & Biotechnol
Keywords:	Destruxin B Human colorectal carcinoma Apoptosis Migration and invasion Wnt-signaling pathway In vivo bioluminescence
Date:	2012-05
Issue Date:	2013-02-21 10:56:50 (UTC+8)
Abstract:	In continuation to our studies toward the identification of direct anti-cancer targets, here we showed that destruxin B (DB) from Metarhizium anisopliae suppressed the proliferation and induced cell cycle arrest in human colorectal cancer (CRC) HT29, SW480 and HCT116 cells. Additionally, DB induced apoptosis in HT29 cells by decreased expression level of anti-apoptotic proteins Bcl-2 and Bcl-xL while increased proapoptotic Bax. On the other hand, DB attenuated Wnt-signaling by downregulation of beta-catenin, Tcf4 and beta-catenin/Tcf4 transcriptional activity, concomitantly with decreased expression of beta-catenin target genes cyclin D1, c-myc and survivin. Furthermore, DB affected the migratory and invasive ability of HT29 cells through suppressed MMPs-2 and -9 enzymatic activities. We also found that DB targeted the MAPK and/or PI3K/Akt pathway by reduced expression of Akt, IKK-alpha, JNK, NF-kappa B, c-Jun and c-Fos while increased that of I kappa B alpha. Finally, we demonstrated that DB inhibited tumorigenesis in HT29 xenograft mice using non-invasive bioluminescence technique. Consistently, tumor samples from DB-treated mice demonstrated suppressed expression of beta-catenin, cyclin D1, survivin, and endothelial marker CD31 while increased caspase-3 expression. Collectively, our data supports DB as an inhibitor of Wnt/beta-catenin/Tcf signaling pathway that may be beneficial in the CRC management. (C) 2012 Elsevier Inc. All rights reserved.
Relation:	TOXICOLOGY AND APPLIED PHARMACOLOGY 卷: 261 期: 1 頁數: 31-41
Appears in Collections:	[Department of Horticulture] journal articles

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