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Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage by upregulating the DNA repair system

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Abstract

Oxidative stress caused by reactive oxygen species (ROS) induces DNA base modifications and DNA strand breaks. In this study, the protective effect of baicalein against H2O2-induced DNA damage was investigated in V79-4 Chinese hamster fibroblast cells. H2O2 treatment increased the levels of intracellular ROS and DNA double-strand breaks (DSBs) and decreased the level of Ku70 protein and the phosphorylation (activation) of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which are involved in the repair of DSBs by nonhomologous end joining. Baicalein effectively scavenged intracellular ROS induced by H2O2, reduced DSBs, and rescued Ku70 protein level and phosphorylation of DNA-PKcs. In cellular response to DNA base damage, 8-oxoguanine DNA glycosylase 1 (OGG1) plays a vital role in the removal of 8-oxoguanine (8-OxoG), which is formed mainly by oxidative stress. Baicalein significantly decreased the levels of 8-OxoG induced by H2O2, and this correlated with increases in OGG1 promoter activity and OGG1 mRNA and protein expression. The phosphorylated form of Akt kinase, which is a regulator of OGG1, was sharply decreased by H2O2, but was prevented by baicalein. A specific Akt inhibitor abolished the cytoprotective effects of baicalein, suggesting that OGG1 induction by baicalein involves the Akt pathway. In conclusion, baicalein exerted protective effects against DNA damage induced by oxidative stress by activating DNA repair systems and scavenging ROS.

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Abbreviations

ROS:

Reactive oxygen species

DSBs:

Double-strand breaks

NHEJ:

Nonhomologous end joining

HR:

Homologous recombination

BER:

Base excision repair

OGG1:

8-Oxoguanine DNA glycosylase 1

DNA-PKcs:

DNA-dependent protein kinase catalytic subunit

PI3K:

Phosphoinositide 3-kinase

8-OhdG:

8-Hydroxy-2-deoxyguanosine

8-OxoG:

8-Oxoguanine

DCF-DA:

2,7-Dichlorodihydrofluorescein diacetate

MTT:

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

TRITC:

Tetramethylrhodamine isothiocyanate

TUNEL:

Terminal deoxynucleotidyl transferase-mediated deoxyUTP nick end labeling

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Acknowledgments

This work was funded by the Ministry of Education, Science and Technology (MEST) of the Republic of Korea (2012R1A1A2005350).

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Authors and Affiliations

  1. School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju, 690-756, Republic of Korea

    Ki Cheon Kim, Kyoung Ah Kang & Jin Won Hyun

  2. Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea

    In Kyung Lee

  3. Cancer Research Institute, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea

    Hye Sun Kim

  4. College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea

    Sam Sik Kang

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  1. Ki Cheon Kim
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  2. In Kyung Lee
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Correspondence to Jin Won Hyun.

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Ki Cheon Kim and In Kyung Lee contributed equally to this study.

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Kim, K.C., Lee, I.K., Kang, K.A. et al. Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage by upregulating the DNA repair system. Cell Biol Toxicol 28, 421–433 (2012). https://doi.org/10.1007/s10565-012-9233-y

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