2002 Fiscal Year Final Research Report Summary
Radical Production and Apoptosis of Eugenol-Related Compounds
| Project/Area Number |
13672119
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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 |
Surgical dentistry
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| Research Institution | Meikai University |
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Principal Investigator |
OKADA Norihisa School of Dentistry, Oral Diagnosis, Assistant Professor, 歯学部, 講師 (40146220)
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| Co-Investigator(Kenkyū-buntansha) |
FUJISAWA Seiichiro School of Dentistry, Oral Diagnosis, Professor, 歯学部, 教授 (40014162)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Methoxyphenol / Eugenol / Radical-induced cytotoxicity / Apoptosis / McSOD / Cu / ZnSOD / Catalytic effect / Caspase |
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| Research Abstract |
We investigated synthesized eugenol related compound-induced cytotoxicity and apoptosis against human cancer cells (HSC-2, HSC-3, HSG and HL-60 cells). 2-methoxy-4-allylphenol (eugenol, EUG), 2-methoxy-4-methylphenol (MMP) and their dimers (bis-EUG, bis-MMP) showed the increasing cytotoxicity with increasing hydrophobicity (log P). Whereas the cytotoxicity of 2-t-butyl-4-metylphenol and its dimers (bis-BHA) and 2, 6-t-butyl-4-methoxyphenol were decreased by increasing hydrophobicity. These findings might be connected with the chemical structure of bulky functional substitutes of 2-t-butyl group. HL-60 cells alone underwent DNA fragmentation and the degree of fragmentation for BHA was greater than that for EUG. In dimers, bis-EUG caused DNA fragmentation at a lower concentration and its Cu/ZnSOD activity in HL-60 cells was significantly larger than MnSOD counterpart. Next, we examined the appearance of mRNA in SOD elements during an apoptosis process using RT-PCR method. MnSOD and Cu/ZnSOD mRNA were found when the concentration of EUG was two-fold greater than that of CC50, possibly due to apoptosis. Also, we examined the cytotoxicity of EUG in the presence of antioxidants with SH-groups such as glutathione, glutathione ethyl ester and cysteine. Antioxidant with SH-groups enhanced the cytotoxicity of EUG, suggesting that EUG acts as a prooxidant. Caspase activations of HL-60 cells induced by EUG with the antioxidants were investigated, resulting in that it activated both exogenous and endogenous paths, and consequently activated caspase-3. However, during activation, EUG having antioxidants with SH-groups may induce not only apoptosis but also necrosis.
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