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    Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response.

    • Authors:
    • Xin Yao
      Nanjing University of Chinese Medicine
      China
      Xian Cheng
      Nagoya University Graduate School of Medicine
      Li Zhang
      Dongfang Hospital Affiliated to Beijing University of Chinese Medicine
      China
      Huixin Yu
      Key Laboratory of Nuclear Medicine
      China
      Jiandong Bao
      Zhejiang University
      China
      Haixia Guan
      Institute of Endocrinology
      Rongrong Lu
      Chongqing Center for Disease Control and Prevention
    Nutr Res 2017 Nov 18;47:63-71. Epub 2017 Sep 18.
    School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China. Electronic address:
    Punicalagin (PUN), a component derived from pomegranate, is well known for its anticancer activity. Our previous work revealed that PUN induces autophagic cell death in papillary thyroid carcinoma cells. We hypothesized that PUN triggers DNA damage associated with cell death because DNA damage was reported as an inducer of autophagy. Our results showed that PUN treatment caused DNA breaks as evidenced by the significant enhancement in the phosphorylation of H2A.X. However, reactive oxygen species and DNA conformational alteration, 2 common inducing factors in DNA damage, were not involved in PUN-induced DNA damage. The phosphorylation of ataxia-telangiectasia mutated gene-encoded protein (ATM) but not ataxia telangiectasia and Rad3-related protein (ATR) was up-regulated in a time- and dosage-dependent manner after PUN treatment. KU-55933, an inhibitor of ATM, inhibited the phosphorylation of ATM induced by PUN and reversed the decreased cell viability caused by PUN. Thus, we demonstrated that PUN induces cell death of papillary thyroid carcinoma cells by triggering ATM-mediated DNA damage response, which provided novel mechanisms and potential targets for the better understanding of the anticancer actions of PUN.
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