Dietary flavonoid apigenin is a potential inducer of intracellular oxidative stress: The role in the interruptive apoptotic signal

Noriyuki Miyoshi, Kisa Naniwa, Takayo Yamada, Toshihiko Osawa, Yoshimasa Nakamura

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Apigenin is a representative dietary flavone (2-phenyl-4H-1-benzopyran-4-one) inhibiting cancer cell growth both in cell culture systems and in vivo. The prooxidant potential of apigenin was confirmed by the observations using flowcytometric and immunoblotting techniques that the intracellular accumulations of reactive oxygen species (ROS) and protein carbonyls were detected in the cells treated with apigenin in a dose-dependent manner. Conversely, chrysin (5,7-dihydroxyflavone) did not show any prooxidant effect. A structure-activity relationship data thus indicated that a 4′-monohydroxyl group, which can be oxidized to semiquinone radical but not up to quinone-like metabolite, is essential for prooxidant effect. When HL-60 cells were treated with not only a heme synthesis inhibitor succinyl acetone (SA) but also myeloperoxidase (MPO) inhibitors, the ROS level enhanced by apigenin was significantly reduced. The gathered data suggested that peroxidase-catalyzed production of apigenin B-ring phenoxyl radicals might be responsible for the prooxidant effect. This is supported by the observation that MPO is able to catalyze production of apigenin phenoxyl radicals, detected by an electron spin resonance-spin trapping technique. We also reveal that both SA and α-tocopherol enhance cellular susceptibility to apoptosis-inducing stimuli by apigenin. In conclusion, the prooxidant effect of apigenin is likely to oxidize a variety of thiols through the formation of phenoxyl radicals and thus seems to play a significant role in the abortive apoptotic pathway switching to necrotic cell death.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume466
Issue number2
DOIs
Publication statusPublished - Oct 15 2007

Fingerprint

Apigenin
Oxidative stress
Flavonoids
Oxidative Stress
Peroxidase
flavone
Acetone
Reactive Oxygen Species
Spin Trapping
Tocopherols
HL-60 Cells
Electron Spin Resonance Spectroscopy
Cell growth
Cell death
Structure-Activity Relationship
Metabolites
Heme
Cell culture
Immunoblotting
Sulfhydryl Compounds

Keywords

  • α-Tocopherol
  • Apigenin
  • Apoptosis
  • Myeloperoxidase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Dietary flavonoid apigenin is a potential inducer of intracellular oxidative stress : The role in the interruptive apoptotic signal. / Miyoshi, Noriyuki; Naniwa, Kisa; Yamada, Takayo; Osawa, Toshihiko; Nakamura, Yoshimasa.

In: Archives of Biochemistry and Biophysics, Vol. 466, No. 2, 15.10.2007, p. 274-282.

Research output: Contribution to journalArticle

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