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Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/β‐catenin pathway
Author(s) -
Li LinNa,
Zhang HuaDong,
Yuan ShouJun,
Tian ZengYue,
Wang Lin,
Sun ZhiXian
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22804
Subject(s) - wnt signaling pathway , colorectal cancer , catenin , apoptosis , cancer research , flow cytometry , cell growth , metastasis , in vivo , growth inhibition , immunofluorescence , mtt assay , biology , signal transduction , medicine , cancer , microbiology and biotechnology , immunology , antibody , biochemistry
Artesunate (ART), a remarkable antimalarial agent, also inhibited the growth of human colorectal carcinoma. As determined by MTT assay, flow cytometry analysis on apoptosis and indirect immunofluorescence analysis on the proliferation‐associated marker Ki67, ART suppressed the proliferation and promoted the apoptosis of colorectal cancer cells in a dose‐dependent manner. Furthermore, immunofluorescence analysis on β‐catenin and RT‐PCR analysis on Wnt/β‐catenin target genes demonstrated ART translocated β‐catenin from nucleus to adherent junctions of membrane and reduced transcription mediated by β‐catenin. These results suggested the anticancer activity of ART correlated with the inhibition of hyperactive Wnt/β‐catenin signaling pathway. In vivo , ART significantly slowed the growth of colorectal tumor xenografts. Bioluminescent imaging also revealed that ART decreased the physiological activity of tumor xenografts and delayed spontaneous liver metastasis. These antitumor effects were related to the membranous translocation of β‐catenin and the inhibition of the unrestricted activation of Wnt/β‐catenin pathway, which was confirmed by the immunohistochemical staining of tumor tissues. These results and the known low toxicity are clues that ART might be a promising candidate drug for the treatment of colorectal carcinoma. © 2007 Wiley‐Liss, Inc.