J Cancer Prev.  2016 Mar;21(1):66-72. 10.15430/JCP.2016.21.1.66.

Ethanol Extract of Cirsium japonicum var. ussuriense Kitamura Exhibits the Activation of Nuclear Factor Erythroid 2-Related Factor 2-dependent Antioxidant Response Element and Protects Human Keratinocyte HaCaT Cells Against Oxidative DNA Damage

• Yoo OK
• Choi BY
• Park JO
• Lee JW
• Park BK
• Joo CG
• Heo HJ
• Keum YS

• KMID: 2161526
• DOI: http://doi.org/10.15430/JCP.2016.21.1.66

Abstract

Keratinocytes are constantly exposed to extracellular insults, such as ultraviolet B, toxic chemicals and mechanical stress, all of which can facilitate the aging of keratinocytes via the generation of intracellular reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in protecting keratinocytes against oxidants and xenobiotics by binding to the antioxidant response element (ARE), a cis-acting element existing in the promoter of most phase II cytoprotective genes. In the present study, we have attempted to find novel ethanol extract(s) of indigenous plants of Jeju island, Korea that can activate the Nrf2/ARE-dependent gene expression in human keratinocyte HaCaT cells. As a result, we identified that ethanol extract of Cirsium japonicum var. ussuriense Kitamura (ECJUK) elicited strong stimulatory effect on the ARE-dependent gene expression. Supporting this observation, we found that ECJUK induced the expression of Nrf2, hemoxygenase-1, and NAD(P)H:quinone oxidoreductase-1 and this event was correlated with Akt1 phosphorylation. We also found that ECJUK increased the intracellular reduced glutathione level and suppressed 12-O-tetradecanoylphorbol acetate-induced 8-hydroxyguanosine formation without affecting the overall viability. Collectively, our results provide evidence that ECJUK can protect against oxidative stress-mediated damages through the activation of Nrf2/ARE-dependent phase II cytoprotective gene expression.

Keyword

Ethanol extract of Cirsium japonicum var. ussuriense Kitamura; Reactive oxygen species; Nuclear factor erythroid 2-related factor 2; Antioxidant response elements

MeSH Terms

Aging
Antioxidant Response Elements*
Cirsium*
DNA Damage*
DNA*
Ethanol*
Gene Expression
Glutathione
Humans*
Keratinocytes*
Korea
Oxidants
Phosphorylation
Reactive Oxygen Species
Stress, Mechanical
Transcription Factors
Xenobiotics
DNA
Ethanol
Glutathione
Oxidants
Reactive Oxygen Species
Transcription Factors
Xenobiotics