PMID- 15525795
OWN - NLM
STAT- MEDLINE
DCOM- 20050405
LR  - 20211203
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 312
IP  - 3
DP  - 2005 Mar
TI  - YC-1 [3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl Indazole] exhibits a novel 
      antiproliferative effect and arrests the cell cycle in G0-G1 in human 
      hepatocellular carcinoma cells.
PG  - 917-25
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 
      G(1) phase arrest in the cell cycle, as detected by an increase in the proportion 
      of cells in the G(1) 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, p21(CIP1/WAP1), and a modest increase in 
      p27(KIP1). The association of p21(CIP1/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 p21(CIP1/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 p21(CIP1/WAP1) expression in HA22T cells. Because of this, YC-1 is a potential 
      antitumor agent worthy of further investigation.
FAU - Wang, Shih-Wei
AU  - Wang SW
AD  - Pharmacological Institutes, College of Medicine, National Taiwan University, 1 
      Jen-Ai Road, Sect. 1, Taipei, Taiwan.
FAU - Pan, Shiow-Lin
AU  - Pan SL
FAU - Guh, Jih-Hwa
AU  - Guh JH
FAU - Chen, Hui-Ling
AU  - Chen HL
FAU - Huang, Dong-Ming
AU  - Huang DM
FAU - Chang, Ya-Ling
AU  - Chang YL
FAU - Kuo, Sheng-Chu
AU  - Kuo SC
FAU - Lee, Fang-Yu
AU  - Lee FY
FAU - Teng, Che-Ming
AU  - Teng CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041103
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Indazoles)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Carcinoma, Hepatocellular/*drug therapy/pathology
MH  - Cell Cycle Proteins/analysis
MH  - Cell Proliferation/drug effects
MH  - Cyclic GMP/physiology
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - DNA-Binding Proteins/physiology
MH  - *G1 Phase
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Indazoles/*pharmacology
MH  - Liver Neoplasms/*drug therapy/pathology
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Nuclear Proteins/physiology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - *Resting Phase, Cell Cycle
MH  - Transcription Factors/physiology
MH  - Tumor Suppressor Proteins/analysis
EDAT- 2004/11/05 09:00
MHDA- 2005/04/06 09:00
CRDT- 2004/11/05 09:00
PHST- 2004/11/05 09:00 [pubmed]
PHST- 2005/04/06 09:00 [medline]
PHST- 2004/11/05 09:00 [entrez]
AID - jpet.104.077230 [pii]
AID - 10.1124/jpet.104.077230 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2005 Mar;312(3):917-25. doi: 10.1124/jpet.104.077230. Epub 
      2004 Nov 3.