| Co-Investigator(Kenkyū-buntansha) |
KUZUHARA Takashi Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Laboratory of Biochemistry, Associate Professor, 薬学部, 助教授 (00260513)
SUENAGA Midori Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Laboratory of Biochemistry, Assistant, 薬学部, 助手 (00389181)
山中 浩泰 徳島文理大学, 薬学部, 助教授 (30202386)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
We previously reported that cotreatment with (-)-epigallocatechin gallate (EGCG) and sulindac, a COX2 inhibitor, induced up-regulated expression of GADD 153 and WAF1 genes dramatically (about 12 times and 3 times), and also induced down-regulated expression of T-plasminogen activator, TIMP3, IL-1β and integrin β4 genes, all less than 0.3 times in human lung cancer cell line PC-9.
1.Cotreatment with EGCG and retinoids
We studied whether cotreatment with EGCG and retinoids would induce also synergistic up-regulation of GADD 153 gene in PC-9 cells. The results are as follows :
EGCG+ATRA, Enhancement(times)5.0
EGCG+9-cis-RA, Enhancement(times)4.9
EGCG+4HPR, no enhancement
The results suggest that the adverse effects of retinoids can be reduced by drinking green tea.
2.Cotreatment with EGCG and gefitinib
It is reported that the efficacy of gefitinib for Japanese is 3 times higher than that for westerners. Since EGCG inhibits the tyrosine-phosphorylation of EGFR, as does gefitinib, we looked at whet
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her cotreatment would induce synergistic inhibition of cell growth :
1)Synergistic inhibition was observed in human lung cancer cell lines, PC-9 and A549.
2)Cotreatment synergistically inhibited the phosphorylation of tyrosine residue in EGFR.
3)Cotreatment synergistically induced apoptosis in PC-9 cells.
3.The discovery of alkyl gallate as a new anticancer agent
Based on our evidence that EGCG induces synergistic anticancer effects with sulindac, celecoxib, ATRA, 9-cis-RA, and gefitinib, we think that the expression of GADD 153 gene can be respectfully used as a biomarker for screening of new anticancer agents.
Treatments with octyl gallate, nonyl gallate and lauryl gallate induced GADD 153 gene expression 10.2,13.4 and 6.4 times, and WAF1 gene expression 19.9,24,0 and 19.2 times, in PC-9 cells, whereas cotreatment with EGCG and sulindac induced GADD 153 gene expression 11.6 times. Since both lauryl and nonyl gallate alone showed potencies similar to that of EGCG with sulindac, we think it would be worthwhile to further investigate alkyl gallate as a new anticancer agent. Less
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