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

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)524-535
Number of pages12
JournalJournal of Nutritional Biochemistry
Volume19
Issue number8
DOIs
Publication statusPublished - 01-08-2008

Fingerprint

U937 Cells
HL-60 Cells
Cell growth
Apoptosis
Growth
Acetylcysteine
Cyclosporine
Cell death
Cytosol
Oxidation-Reduction
Cysteine
allicin
Cell Death
Chemical activation
Cells
Buthionine Sulfoximine
Garlic
Mitochondria
Glutathione Disulfide
Caspase 9

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Miron, Talia ; Wilchek, Meir ; Sharp, Ayala ; Nakagawa, Yoshihito ; Naoi, Makoto ; Nozawa, Yoshinori ; Akao, Yukihiro. / Allicin inhibits cell growth and induces apoptosis through the mitochondrial pathway in HL60 and U937 cells. In: Journal of Nutritional Biochemistry. 2008 ; Vol. 19, No. 8. pp. 524-535.
@article{2aef91a4efef41b296377d565836e1e3,
title = "Allicin inhibits cell growth and induces apoptosis through the mitochondrial pathway in HL60 and U937 cells",
abstract = "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.",
author = "Talia Miron and Meir Wilchek and Ayala Sharp and Yoshihito Nakagawa and Makoto Naoi and Yoshinori Nozawa and Yukihiro Akao",
year = "2008",
month = "8",
day = "1",
doi = "10.1016/j.jnutbio.2007.06.009",
language = "English",
volume = "19",
pages = "524--535",
journal = "Journal of Nutritional Biochemistry",
issn = "0955-2863",
publisher = "Elsevier Inc.",
number = "8",

}

Allicin inhibits cell growth and induces apoptosis through the mitochondrial pathway in HL60 and U937 cells. / Miron, Talia; Wilchek, Meir; Sharp, Ayala; Nakagawa, Yoshihito; Naoi, Makoto; Nozawa, Yoshinori; Akao, Yukihiro.

In: Journal of Nutritional Biochemistry, Vol. 19, No. 8, 01.08.2008, p. 524-535.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Allicin inhibits cell growth and induces apoptosis through the mitochondrial pathway in HL60 and U937 cells

AU - Miron, Talia

AU - Wilchek, Meir

AU - Sharp, Ayala

AU - Nakagawa, Yoshihito

AU - Naoi, Makoto

AU - Nozawa, Yoshinori

AU - Akao, Yukihiro

PY - 2008/8/1

Y1 - 2008/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=46749116520&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46749116520&partnerID=8YFLogxK

U2 - 10.1016/j.jnutbio.2007.06.009

DO - 10.1016/j.jnutbio.2007.06.009

M3 - Article

VL - 19

SP - 524

EP - 535

JO - Journal of Nutritional Biochemistry

JF - Journal of Nutritional Biochemistry

SN - 0955-2863

IS - 8

ER -