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This knowledge has triggered searches for \u201cepigenetic drugs\u201d that can be developed into new cancer therapies. Here we report that triptolide reduced lung cancer incidence from 70% to 10% in a Fen1 E160D transgenic mouse model and effectively inhibited cancer growth and metastasis in A549 and H460 mouse xenografts. We found that triptolide induced lung cancer cell apoptosis that was associated with global epigenetic changes to histone 3 (H3). These global epigenetic changes in H3 are correlated with an increase in protein expression of five Wnt inhibitory factors that include WIF1, FRZB, SFRP1, ENY2, and DKK1. Triptolide had no effect on DNA methylation status at any of the CpG islands located in the promoter regions of all five Wnt inhibitory factors. Wnt expression is implicated in promoting the development and progression of many lung cancers. Because of this, the potential to target Wnt signaling with drugs that induce epigenetic modifications provides a new avenue for developing novel therapies for patients with these tumor types.<\/jats:p>","DOI":"10.1002\/ijc.31756","type":"journal-article","created":{"date-parts":[[2018,7,14]],"date-time":"2018-07-14T08:40:50Z","timestamp":1531557650000},"page":"2470-2478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Triptolide inhibits Wnt signaling in NSCLC through upregulation of multiple Wnt inhibitory factors via epigenetic modifications to Histone H3"],"prefix":"10.1002","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-9917","authenticated-orcid":false,"given":"Isaac","family":"Nardi","sequence":"first","affiliation":[{"name":"City of Hope Medical Center, Division of Thoracic Surgery, Baum Family Thoracic Oncology laboratory; Beckman Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Reno","sequence":"additional","affiliation":[{"name":"City of Hope Medical Center, Division of Thoracic Surgery, Baum Family Thoracic Oncology laboratory; 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