2003 Fiscal Year Final Research Report Summary
Molecular mechanism of cancer chemoprevention by anthocyanins
| Project/Area Number |
13660130
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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 |
食品科学・栄養科学
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| Research Institution | Kagoshima University |
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Principal Investigator |
HOU De-xing Kagoshima University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90305160)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Makoto Kagoshima University, Faculty of Agriculture, Professor, 農学部, 教授 (70041655)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Anthocyanins / Functional food / molecular nutrition / Apoptosis / Reactive oxygen species / JNK / c-jun / Caspases |
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| Research Abstract |
Anthocyanidins are the aglycon nucleuses of anthocyanins, which are reddish pigments widely spread in colored fruits and vegetables. To investigate the anti-cancer effect of anthocyanins, induction of apoptosis was tested in human promyelocytic leukemia cells (HL-60), which is a valid model for testing antileukemic or general antitumoral compounds. Of six anthocyanidins representing the aglycons of most of anthocyanins, only those with an ortho-dihydroxyphenyl structure on the B-ring induce apoptosis, suggesting that the ortho-dihydroxyphenyl structure of anthocyanidins may contribute to the induction of apoptosis. Delphinidin, the most potent inducer, causes apoptosis in a time-and dose-dependent manner. The efficacious induction of apoptosis was observed at 100 μM for 6 h. Concomitant with the apoptosis, delphinidin stimulates JNK pathway activation including JNK phosphorylation and c-jun gene expression, and activates caspase-3. Antioxidants including N-acetyl-L-cysteine (NAC) and catalase effectively block delphinidin-induced JNK phosphorylation, caspase-3 activation, and DNA fragmentation. Moreover, anthocyanidins directly cause HL-60 cells to generate intracellular hydrogen peroxide. Thus, anthocyanidins may trigger an apoptotic death program through an oxidative stress-involved JNK signaling pathway. The induction of apoptosis by anthocyanins may be the pivotal mechanism by which its chemopreventive action against cancer is based.
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