Allicin inhibits cell growth and induces apoptosis through the mitochondrial pathway in HL60 and U937 cells

Talia Miron, Meir Wilchek, Ayala Sharp, Yoshihito Nakagawa, Makoto Naoi, Yoshinori Nozawa, Yukihiro Akao

研究成果: Article査読

71 被引用数 (Scopus)

抄録

In this article, the effects of allicin, a biological active compound of garlic, on HL60 and U937 cell lines were examined. Allicin induced growth inhibition and elicited apoptotic events such as blebbing, mitochondrial membrane depolarization, cytochrome c release into the cytosol, activation of caspase 9 and caspase 3 and DNA fragmentation. Pretreatment of HL60 cells with cyclosporine A, an inhibitor of the mitochondrial permeability transition pore (mPTP), inhibited allicin-treated cell death. HL60 cell survival after 1 h pretreatment with cyclosporine A, followed by 16 h in presence of allicin (5 μM) was ∼80% compared to allicin treatment alone (∼50%). Also N-acetyl cysteine, a reduced glutathione (GSH) precursor, prevented cell death. The effects of cyclosporine A and N-acetyl cysteine suggest the involvement of mPTP and intracellular GSH level in the cytotoxicity. Indeed, allicin depleted GSH in the cytosol and mitochondria, and buthionine sulfoximine, a specific inhibitor of GSH synthesis, significantly augmented allicin-induced apoptosis. In HL60 cells treated with allicin (5 μM, 30 min) the redox state for 2GSH/oxidized glutathione shifted from EGSH -240  to -170 mV. The same shift was observed in U937 cells treated with allicin at a higher concentration for a longer period of incubation (20 μM, 2 h). The apoptotic events induced by various concentrations of allicin correlate to intracellular GSH levels in the two cell types tested (HL60: 3.7 nmol/106 cells; U937: 7.7 nmol/106 cells). The emerging mechanistic basis for the antiproliferative function of allicin, therefore, involves the activation of the mitochondrial apoptotic pathway by GSH depletion and by changes in the intracellular redox status.

本文言語English
ページ(範囲)524-535
ページ数12
ジャーナルJournal of Nutritional Biochemistry
19
8
DOI
出版ステータスPublished - 08-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子生物学
  • 栄養および糖尿病
  • 臨床生化学

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