https://scholars.lib.ntu.edu.tw/handle/123456789/564861
標題: | YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] exhibits a novel antiproliferative effect and arrests the cell cycle in G 0-G1 in human hepatocellular carcinoma cells | 作者: | Wang S.-W. Pan S.-L. JIH-HWA GUH Chen H.-L. Huang D.-M. Chang Y.-L. Kuo S.-C. Lee F.-Y. Teng C.-M. |
公開日期: | 2005 | 卷: | 312 | 期: | 3 | 起(迄)頁: | 917-925 | 來源出版物: | Journal of Pharmacology and Experimental Therapeutics | 摘要: | This study delineates the antiproliferative activities and in vivo efficacy of YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] in human hepatocellular carcinoma cells. YC-1 inhibited the growth of HA22T and Hep3B cells in a concentration-dependent manner without significant cytotoxicity. YC-1 induced G1 phase arrest in the cell cycle, as detected by an increase in the proportion of cells in the G1 phase using FAC-Scan flow cytometric analysis. It was further shown that cGMP, p42/p44 mitogen-activated protein kinase, or AKT kinase-mediated signaling pathways did not contribute to the YC-1-induced effect. Of note, YC-1 induced a dramatic increase in the expression of cyclin-dependent kinase (CDK)-inhibitory protein, p21CIP1/WAP1, and a modest increase in p27KIP1. The association of p21CIP1/WAP1 with CDK2 was markedly increased in cells responsive to YC-1. YC-1 did not modify the expression of cyclin D1, cyclin E, CDK2, or CDK4. In a corollary in vivo study, YC-1 induced dose-dependent inhibition of tumor growth in mice inoculated with HA22T cells. Immunohistochemical analysis revealed an inverse relationship between the staining of p21CIP1/WAF and the staining of Ki-67, a cell proliferation marker. Based on the results reported herein, we suggest that YC-1 induces cell cycle arrest and inhibits tumor growth both in vitro and in vivo via the up-regulation of p21CIP1/WAP1 expression in HA22T cells. Because of this, YC-1 is a potential anti-tumor agent worthy of further investigation. Copyright ? 2005 by The American Society for Pharmacology and Experimental Therapeutics. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-14344254896&doi=10.1124%2fjpet.104.077230&partnerID=40&md5=d4d217089b41b126ec612dc7d128a3ea https://scholars.lib.ntu.edu.tw/handle/123456789/564861 |
ISSN: | 223565 | DOI: | 10.1124/jpet.104.077230 | SDG/關鍵字: | 1 benzyl 3 (5 hydroxymethyl 2 furyl)indazole; cyclic GMP; cyclin D1; cyclin dependent kinase; cyclin dependent kinase 2; cyclin dependent kinase 4; cyclin dependent kinase inhibitor 1; cyclin dependent kinase inhibitor 1B; cyclin E; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein kinase B; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer growth; cancer inhibition; cancer survival; carcinoma cell; cell cycle G0 phase; cell cycle G1 phase; cell cycle S phase; cell proliferation; concentration response; controlled study; cytostasis; cytotoxicity; drug activity; drug efficacy; flow cytometry; human; human cell; immunohistochemistry; liver cell carcinoma; male; mouse; nonhuman; priority journal; protein expression; protein phosphorylation; signal transduction; tumor xenograft; upregulation; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Cycle Proteins; Cell Proliferation; Cyclic GMP; Cyclin-Dependent Kinase Inhibitor p27; DNA-Binding Proteins; G0 Phase; G1 Phase; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Indazoles; Liver Neoplasms; Mitogen-Activated Protein Kinase 1; Nuclear Proteins; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Transcription Factors; Tumor Suppressor Proteins |
顯示於: | 藥學系 |
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