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PGA2 induces the expression of HO-1 by activating p53 in HCT116 cells

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Abstract

Prostaglandin (PG) A2 which is a cytotoxic PG, was reported to induce the expression of heme oxygenase (HO)-1 via activation of p38MAPK to keep U2OS cells from cell cycle arrest in G2M phase. The expression of HO-1 is primarily regulated at the level of transcription. But the transcription factors that are responsible for PGA2-induced HO-1 expression were not clarified yet. Here, we report that PGA2-induced transcription of HO-1 is mediated by p53, a tumor suppressive transcription factor. In HCT116 cells, PGA2 treatment led to the phosphorylation of p53 and an increase of p21WAF1 transcription as well as the activation of HO-1 transcription. Knocking p53 down via RNA interference or inhibiting the p53’s transcriptional activity by pifithrin-α treatment led to suppression of the increase in the level of both HO-1 expression and activity of HO-1 promoter. Pretreatment of NU-7441, a chemical inhibitor of DNA-activated protein kinase (DNA-PK), prevented both the PGA2-induced phosphorylation of p53 and an increase of HO-1 transcription. In addition, N-acetyl-l-cysteine, a scavenger of reactive oxygen species (ROS), also mimicked the effect of NU-7441 on the PGA2-induced activation of p53 and HO-1 transcription. Collectively, these results suggest that PGA2 induces the expression of HO-1 via activation of p53, which is mediated by the ROS-DNA-PK pathway.

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Authors and Affiliations

  1. Department of Biochemistry, The Catholic University of Korea, Seoul, 06591, Republic of Korea

    Hyein Lee, Sang-Sun Lee, Ji-Young Park, Yun-Jeong Choe, Sun-Young Lee & Ho-Shik Kim

  2. Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea

    Hyein Lee, Sang-Sun Lee & Ji-Young Park

  3. Department of Biology, Faculty of Science, Naresuan University, Phitsanulok, 65000, Thailand

    Sun-Young Lee

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  1. Hyein Lee
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Correspondence to Ho-Shik Kim.

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Lee, H., Lee, SS., Park, JY. et al. PGA2 induces the expression of HO-1 by activating p53 in HCT116 cells. Mol. Cell. Toxicol. 13, 189–196 (2017). https://doi.org/10.1007/s13273-017-0020-y

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  • DOI: https://doi.org/10.1007/s13273-017-0020-y

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