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Article Publish Status: FREE
Abstract Title:

Anti-Tumorigenic Activity of Chrysin fromvia Non-Genotoxic p53 Activation through the ATM-Chk2 Pathway.

Abstract Source:

Molecules. 2018 Jun 8 ;23(6). Epub 2018 Jun 8. PMID: 29890668

Abstract Author(s):

Mai Nagasaka, Ryoko Hashimoto, Yasumichi Inoue, Kan'ichiro Ishiuchi, Michiyo Matsuno, Yuka Itoh, Muneshige Tokugawa, Nobumichi Ohoka, Daisuke Morishita, Hajime Mizukami, Toshiaki Makino, Hidetoshi Hayashi

Article Affiliation:

Mai Nagasaka

Abstract:

The p53 tumor suppressor plays critical roles in cell cycle regulation and apoptotic cell death in response to various cellular stresses, thereby preventing cancer development. Therefore, the activation of p53 through small molecules is an attractive therapeutic strategy for the treatment of cancers retaining wild-type p53. We used a library of 700 Myanmar wild plant extracts to identify small molecules that induce p53 transcriptional activity. A cell-based screening method with a p53-responsive luciferase-reporter assay system revealed that an ethanol extract ofbark increased p53 transcriptional activity. Chrysin was isolated and identified as the active ingredient in thebark extract. A treatment with chrysin increased p53 protein expression and the p53-mediated expression of downstream target genes, and decreased cell viability in MCF7 cells, but not in p53-knockdown MCF7 cells. We also found that chrysin activated the ATM-Chk2 pathway in the absence of DNA damage. Hence, the inactivation of the ATM-Chk2 pathway suppressed p53 activation induced by chrysin. These results suggest the potential of chrysin as an anti-cancer drug through the activation of p53 without DNA damage.

Study Type : In Vitro Study

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Sayer Ji
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