2006 Fiscal Year Final Research Report Summary
Procaine has anti-proliferative effect and functions as an inhibitor of DNA methylation in human hepatocellular carcinoma and gastric cancer
| Project/Area Number |
17590613
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Chiba University |
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Principal Investigator |
FUKAI Kenichi Chiba University Hospital, Department of Gastroenterology, Instructor, 医学部附属病院, 助手 (60361432)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOSUKA Osamu Chiba University, Graduate School of Medcine・Department of Medicine and Clinical Oncology, Professor, 医学部附属病院, 教授 (90182691)
IMAZEKI Fumio Chiba University, Graduate School of Medcine・Department of Medicine and Clinical Oncology, Assistant Professor, 医学部附属病院, 講師 (40223325)
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| Project Period (FY) |
2005 – 2006
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| Keywords | hepatocellular carcinoma / gastric cancer / epigenetic disorder / DNA methylation / transcriptional regulation / anti-cancer agent / demethylating agent / tumor suppressor gene |
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| Research Abstract |
In this study, we revealed that a local anesthetic, procaine (PCA), possessed growth-inhibitory and demethylating effect on human hepatoma cells (HLE, HuH7, HepG2, Hep3B, PLC/PRF/5, HuH6) and gastric cancer cells (AGS, MKN1, MKN45, MKN74, KATOIII) in vitro. The viability of PCA-treated cells with or without trichostatin A (TSA) was assessed by MTS assay and found that the viability of HLE, HuH7, HuH6 and all gastric cancer cells examined was significantly decreased by PCA treatment. In these cells, the combination treatment with TSA and PCA exhibited stronger reduction of the viability. To clarify the mechanism of the anti-proliferating effect of PCA, TUNEL assay, FACS analysis and morphological observation of PCA-treated cells were performed. Inhibition of S/G2/M transition, morphological changes such as vacuolation and no increase in apoptosis rate were observed in the PCA-treated HLE cells. The genes that were transcriptionally suppressed by DNA hypermethylation in hepatoma cells or gastric cancer cells were demonstrated to be demethylated and reactivated after PCA treatment. The growth-inhibitory effect of PCA in vivo was tested in nude mice bearing xenograft and PCA treatment was revealed to lead to a significant reduction in tumor volume in vivo. In conclusion, these data indicated that PCA had growth-inhibitory and demethylating effects on human hepatoma cells and gastric cancer cells in vitro and in vivo. PCA may be a candidate agent for future therapies against HCC and gastric cancer.
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