| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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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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