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γ-Glutamyl-S-allyl-cysteine inhibits hepatic stellate cell proliferation and collagen secretion via a proapoptotic mechanism

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Abstract

We investigated the effects of γ-glutamyl-S-allyl-cysteine (GSAC) on the activated HSC cell line HSC-T6. GSAC inhibited the proliferation of HSC-T6 cells for 24 h with a half inhibitory concentration of 0.084 ± 0.005 mg/mL. FITC–Annexin V/PI double staining revealed that concentrations of 0.02, 0.04, and 0.08 mg/mL GSAC induced apoptosis at rates of 4.72 ± 0.83, 8.56 ± 1.94, and 18.63 ± 0.98 %, respectively. A DNA ladder pattern was observed in cells treated with 0.04 and 0.08 mg/mL GSAC in agarose gel electrophoresis of genomic DNA. The mitochondrial membrane potential decreased and the intracellular reactive oxygen species (ROS) increased in a concentration-dependent manner in GSAC-treated cells. Western blot analyses revealed that GSAC down-regulated TGF-β1, collagen I, and Bcl-2 and up-regulated Bax. GSAC also significantly increased the activities of caspase-3 and caspase-9. These results indicate that GSAC inhibited the proliferation and collagen secretion of HSC-T6 cells and that induction of ROS and apoptosis through a mitochondrial pathway may play important roles in the underlying mechanism.

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Abbreviations

GSAC:

γ-Glutamyl-S-allyl-cysteine

HSC:

Hepatic stellate cell

IC50 :

50 % Inhibitory concentration

MMP:

Mitochondrial membrane potential

ROS:

Reactive oxygen species

ACSOs:

S-alk(en)yl-l-cysteine sulfoxides

DAS:

Diallyl sulfide

DADS:

Diallyl disulfide

DATS:

Diallyl trisulfide

FBS:

Fetal bovine serum

DMEM:

Dulbecco’s modified Eagle’s medium

DCFH-DA:

2,7-Dichlorofluorescein-diacetate

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

EB:

Ethidium bromide

HPLC:

High-performance liquid chromatography

PS:

Phosphatidylserine

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Acknowledgments

Financial support from the grants of National Natural Science Foundation of China (31101220 and 31370685) and State Science and Technology Support Program (2012BAD38B07) is gratefully acknowledged.

Conflict of interest

The authors declare that there are no conflicts of interest.

Compliance with Ethics Requirements

This article does not contain any studies with human or animal subjects.

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    Authors and Affiliations

    1. College of Food, Shenyang Agricultural University, No. 120 Dongling Road, Shenhe District, Shenyang City, 110866, People’s Republic of China

      Bimi Zhang, Dehong Tan, Bing Bai, Yin He & Shujuan Ji

    2. Modern Agricultural college, Jilin Province Economic Management Cadre College, Silicon Valley street No. 429, Changchun City, 130012, People’s Republic of China

      Bimi Zhang

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    1. Bimi Zhang
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    Correspondence to Shujuan Ji.

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    Bimi Zhang and Dehong Tan are co-authors and they have contributed equally to this work.

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    Zhang, B., Tan, D., Bai, B. et al. γ-Glutamyl-S-allyl-cysteine inhibits hepatic stellate cell proliferation and collagen secretion via a proapoptotic mechanism. Eur Food Res Technol 240, 1271–1280 (2015). https://doi.org/10.1007/s00217-015-2453-7

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