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Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure-activity relationship and

De-Xing Hou1, Keiko Kai, Jian-Jian Li

  • 1Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Japan. hou@chem.agri.kagoshima-u.ac.jp

Carcinogenesis
|September 30, 2003
PubMed

Insights

Anthocyanidins, natural compounds in colorful fruits and vegetables, show anticancer potential by inhibiting tumor promotion. They work by blocking specific pathways in cell signaling, offering a molecular basis for their anticarcinogenic effects.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Anthocyanins are natural pigments in fruits and vegetables with known antioxidant properties.
  • Anthocyanidins are the aglycons of anthocyanins and are investigated for their health benefits.
  • Understanding the molecular mechanisms of their anticancer effects is crucial for food-based cancer chemoprevention.

Purpose of the Study:

  • To investigate the mechanism by which anthocyanidins inhibit tumor promotion.
  • To identify specific structural features of anthocyanidins responsible for anticancer activity.
  • To elucidate the molecular pathways targeted by anthocyanidins in cancer chemoprevention.

Main Methods:

  • Tested six types of anthocyanidins on mouse JB6 cells, a model for cancer chemoprevention screening.
  • Assessed the suppression of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation and activator protein-1 (AP-1) transactivation.
  • Analyzed the effects of anthocyanidins on mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK).

Main Results:

  • Anthocyanidins with an ortho-dihydroxyphenyl structure on the B-ring suppressed TPA-induced cell transformation and AP-1 transactivation.
  • Delphinidin inhibited the phosphorylation of ERK and JNK signaling pathways, but not p38 kinase.
  • Specific MAPK inhibitors (SP600125 for JNK, UO126 for ERK) blocked cell transformation, confirming the role of these pathways.

Conclusions:

  • Anthocyanidins inhibit tumor promotion by suppressing MAPK pathway activation.
  • The ortho-dihydroxyphenyl moiety is important for the anticancer activity of anthocyanidins.
  • These findings provide a molecular basis for the anticarcinogenic properties of anthocyanidins found in food sources.

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