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Epigallocatechin-3-gallate regulates the expression of Kruppel-like factor 4 through myocyte enhancer factor 2A

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Cell Stress and Chaperones Aims and scope

Abstract

Epigallocatechin-3-gallate (EGCG), a powerful antioxidant and free ion scavenger found in green tea, exhibits inhibitory effects on different stages of tumorigenesis. Within gastric cancer cells, the transcription factor Kruppel-like factor 4 (KLF4) is downregulated, and it is possible that EGCG exerts its anti-tumorigenic function through modulation of KLF4 expression. In order to examine the effects of EGCG on KLF4 in a gastric tumor model, we treated the gastric cancer cell line NCI-N87 with EGCG. We found that EGCG treatment results in increased expression of KLF4 and alters expression of the KLF4 target genes p21, CDK4, and cyclin D1. EGCG inhibits the growth of NCI-N87 cells in a time- and dose-dependent manner through arresting the cell cycle in the G0/G1 phase. Furthermore, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and 4′,6-diamidino-2-phenylindole staining revealed that EGCG is able to promote apoptosis of NCI-N87 cells. The suppressive effects of EGCG on cell growth and cell cycle protein expression are eliminated by decreasing KLF4 mRNA using siRNA and are magnified by overexpressing KLF4. Using KLF4 reporter constructs, we verified that the elevated expression induced by EGCG was mediated by increasing levels of activated MEF2A, which bound to the promoter region of KLF4. Taken together, this is the first time that EGCG is reported to increase the expression of KLF4, suggesting a novel mechanisms in gastric cancer treatment.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, the Affiliated Hospital of WeiFang Medical University, No. 465 Yuhe Road, Kuiwen District, Weifang City, Shandong, 261031, People’s Republic of China

    Yuwen Ma

  2. Department of Emergency Medicine, the Affiliated Hospital of WeiFang Medical University, No. 465 Yuhe Road, Kuiwen District, Weifang City, Shandong, 261031, People’s Republic of China

    Youkui Shi

  3. Department of Colorectal Surgery, the Affiliated Hospital of WeiFang Medical University, No. 465 Yuhe Road, Kuiwen District, Weifang City, Shandong, 261031, People’s Republic of China

    Wenmei Li

  4. Department of Anesthesia, Qingdao Orthopaedics and Traumatology Hospital, No. 122 Taidong San Road, Qingdao, Shandong, 266021, People’s Republic of China

    Aijuan Sun

  5. Department of Nursing, the Affiliated Hospital of WeiFang Medical University, No. 465 Yuhe Road, Kuiwen District, Weifang City, Shandong, 261031, People’s Republic of China

    Ping Zang

  6. Department of Critical Care Medicine, the Affiliated Hospital of WeiFang Medical University, No. 465 Yuhe Road, Kuiwen District, Weifang City, Shandong, 261031, People’s Republic of China

    Peirong Zhang

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  1. Yuwen Ma
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  2. Youkui Shi
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  3. Wenmei Li
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  4. Aijuan Sun
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  5. Ping Zang
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  6. Peirong Zhang
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Correspondence to Peirong Zhang.

Additional information

Yuwen Ma and Youkui Shi are the co-first authors.

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Ma, Y., Shi, Y., Li, W. et al. Epigallocatechin-3-gallate regulates the expression of Kruppel-like factor 4 through myocyte enhancer factor 2A. Cell Stress and Chaperones 19, 217–226 (2014). https://doi.org/10.1007/s12192-013-0447-6

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  • DOI: https://doi.org/10.1007/s12192-013-0447-6

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