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IR@PKUHSC  > 北京大学药学院  > 天然药物学系  > 期刊论文
学科主题: 药学
题名:
Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging
作者: Yeh, Chi-Tai7,8,9; Rao, Yerra Koteswara6; Ye, Min5; Wu, Wen-Shi4; Chang, Tung-Chen7; Wang, Liang-Shun3,9; Wu, Chih-Hsiung7,8; Wu, Alexander T. H.1,2; Tzeng, Yew-Min6
关键词: Destruxin B ; Human colorectal carcinoma ; Apoptosis ; Migration and invasion ; Wnt-signaling pathway ; In vivo bioluminescence
刊名: TOXICOLOGY AND APPLIED PHARMACOLOGY
发表日期: 2012-05-15
DOI: 10.1016/j.taap.2012.03.007
卷: 261, 期:1, 页:31-41
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
关键词[WOS]: BETA-CATENIN ; STEM-CELLS ; METARHIZIUM-ANISOPLIAE ; CARCINOMA CELLS ; PATHWAY ; ACTIVATION ; EXPRESSION ; CYCLODEPSIPEPTIDES ; PURIFICATION ; GROWTH
英文摘要:

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.

语种: 英语
所属项目编号: NSC 100-2113-M-324-001-MY3 ; NSC 99-2811-M-324-003 ; NSC 99-2628-B-038-010-MY3 ; 100-TMU-TMUH-09 ; NSC 100-2313-B-038-001-MY3 ; DOH99-TD-C-111-008 ; 100-TMU-SHH-07
项目资助者: National Science Council of Taiwan ; Center of Excellence for Cancer Research at Taipei Medical University ; Taipei Medical University
WOS记录号: WOS:000304494600004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51582
Appears in Collections:北京大学药学院_天然药物学系_期刊论文

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作者单位: 1.Taipei Med Univ Hosp, Dept Radiat Oncol, Taipei, Taiwan
2.Taipei Med Univ, Shuang Ho Hosp, Dept Surg, Taipei, Taiwan
3.Taipei Med Univ, Ctr Excellence Canc Res, Taipei, Taiwan
4.Taipei Med Univ, Grad Inst Clin Med, Taipei, Taiwan
5.Taipei Med Univ, Coll Med Sci & Technol, PhD Program Translat Med, Taipei, Taiwan
6.Taipei Med Univ, Shuang Ho Hosp, Dept Surg, Div Thorac Surg, Taipei, Taiwan
7.Chinese Culture Univ, Dept Hort & Biotechnol, Taipei, Taiwan
8.Peking Univ, Sch Pharmaceut Sci, Dept Nat Med, Beijing 100871, Peoples R China
9.Chaoyang Univ Technol, Inst Biochem Sci & Technol, Taichung, Taiwan

Recommended Citation:
Yeh, Chi-Tai,Rao, Yerra Koteswara,Ye, Min,et al. Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2012,261(1):31-41.
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