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Gallic acid-induced lung cancer cell death is accompanied by ROS increase and glutathione depletion

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Abstract

Gallic acid (GA) is generally distributed in a variety of plants and foods, and its various biological effects have been reported. Here, we investigated the effects of GA and/or caspase inhibitors on Calu-6 and A549 lung cancer cells in relation to cell death and reactive oxygen species (ROS). The growths of Calu-6 and A549 cells were diminished with an IC50 of approximately 30 and 150 μM GA at 24 h, respectively. GA also inhibited the growth of primary human pulmonary fibroblast (HPF) cells with an IC50 of about 300 μM. GA induced apoptosis and/or necrosis in lung cancer cells, which was accompanied by the loss of mitochondrial membrane potential (MMP, ΔΨm). The percents of MMP (ΔΨm) loss and death cells by GA were lower in A549 cells than in Calu-6 cells. Caspase inhibitors did not significantly rescued lung cancer cells from GA-induced cell death. GA increased ROS levels including O2 •− and induced GSH depletion in both lung cancer cells. Z-VAD (pan-caspase inhibitor) did not decrease ROS levels and GSH depleted cell number in GA-treated lung cancer cells. In conclusion, GA inhibited the growth of lung cancer and normal cells. GA-induced lung cancer cell death was accompanied by ROS increase and GSH depletion.

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Abbreviations

GA:

Gallic acid

HPF:

Human pulmonary fibroblast

ROS:

Reactive oxygen species

MMP (ΔΨm):

Mitochondrial membrane potential

FBS:

Fetal bovine serum

MTT:

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

PI:

Propidium iodide

FITC:

Fluorescein isothiocyanate

Z-VAD-FMK:

Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone

Z-DEVD-FMK:

Benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone

Z-IETD-FMK:

Benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone

Z-LEHD-FMK:

Benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone

H2DCFDA:

2′,7′-Dichlorodihydrofluorescein diacetate

DHE:

Dihydroethidium

GSH:

Glutathione

CMFDA:

5-Chloromethylfluorescein diacetate

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Acknowledgments

This study was supported by a grant from the Ministry of Science & Technology (MoST)/Korea Science & Engineering Foundation (KOSEF) through the Diabetes Research Center at Chonbuk National University (2010-0029497) and the National Research Foundation of Korea Grant funded by the Korean Government (MEST) (2010-0021808).

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Authors and Affiliations

  1. Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, JeonJu, 561-180, Republic of Korea

    Bo Ra You, Sung Zoo Kim, Suhn Hee Kim & Woo Hyun Park

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  1. Bo Ra You
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  2. Sung Zoo Kim
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  3. Suhn Hee Kim
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  4. Woo Hyun Park
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Correspondence to Woo Hyun Park.

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You, B.R., Kim, S.Z., Kim, S.H. et al. Gallic acid-induced lung cancer cell death is accompanied by ROS increase and glutathione depletion. Mol Cell Biochem 357, 295–303 (2011). https://doi.org/10.1007/s11010-011-0900-8

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  • DOI: https://doi.org/10.1007/s11010-011-0900-8

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