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

Authors:
Xin Yao
Xin Yao
Nanjing University of Chinese Medicine
China
Xian Cheng
Xian Cheng
Nagoya University Graduate School of Medicine
Li Zhang
Li Zhang
Dongfang Hospital Affiliated to Beijing University of Chinese Medicine
China
Huixin Yu
Huixin Yu
Key Laboratory of Nuclear Medicine
China
Jiandong Bao
Jiandong Bao
Zhejiang University
China
Haixia Guan
Haixia Guan
Institute of Endocrinology
Rongrong Lu
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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November 2017
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