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

Shih Wei Wang, Shiow Lin Pan, Jih Hwa Guh, Hui Ling Chen, Dong Ming Huang, Ya Ling Chang, Sheng Chu Kuo, Fang Yu Lee, Che Ming Teng

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)917-925
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume312
Issue number3
DOIs
Publication statusPublished - Mar 2005
Externally publishedYes

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Indazoles
Cell Cycle Checkpoints
Hepatocellular Carcinoma
G1 Phase
Growth
Staining and Labeling
Cyclin E
Neoplasms
Cyclin-Dependent Kinases
Mitogen-Activated Protein Kinase 1
Cyclin D1
Phosphotransferases
Up-Regulation
Cell Proliferation

ASJC Scopus subject areas

  • Pharmacology

Cite this

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. / Wang, Shih Wei; Pan, Shiow Lin; Guh, Jih Hwa; Chen, Hui Ling; Huang, Dong Ming; Chang, Ya Ling; Kuo, Sheng Chu; Lee, Fang Yu; Teng, Che Ming.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 312, No. 3, 03.2005, p. 917-925.

Research output: Contribution to journalArticle

Wang, Shih Wei ; Pan, Shiow Lin ; Guh, Jih Hwa ; Chen, Hui Ling ; Huang, Dong Ming ; Chang, Ya Ling ; Kuo, Sheng Chu ; Lee, Fang Yu ; Teng, Che Ming. / 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. In: Journal of Pharmacology and Experimental Therapeutics. 2005 ; Vol. 312, No. 3. pp. 917-925.
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abstract = "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.",
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T1 - 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

AU - Wang, Shih Wei

AU - Pan, Shiow Lin

AU - Guh, Jih Hwa

AU - Chen, Hui Ling

AU - Huang, Dong Ming

AU - Chang, Ya Ling

AU - Kuo, Sheng Chu

AU - Lee, Fang Yu

AU - Teng, Che Ming

PY - 2005/3

Y1 - 2005/3

N2 - 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.

AB - 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.

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