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Epigenetic regulation of Nrf2 and ursolic acid in skin carcinogenesis
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Ramirez, Christina N.. Epigenetic regulation of Nrf2 and ursolic acid in skin carcinogenesis. Retrieved from https://doi.org/doi:10.7282/t3-rrwe-p725

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TitleEpigenetic regulation of Nrf2 and ursolic acid in skin carcinogenesis
NameRamirez, Christina N. (author); Cai, Li (chair); Liu, Fang (internal member); Kong, Ah-Ng Tony (internal member); Bertino, Joseph (outside member); Rutgers University; School of Graduate Studies
Date Created2018
Other Date2018-10 (degree)
SubjectPharmacology, Cellular and Molecular, Skin -- Cancer, Triterpenoid saponins
Extent1 online resource (122 pages : illustrations)
DescriptionNon-melanoma skin cancer (NMSC) is the most common cancer in the United States with over 4.0 million new cases diagnosed in 2012. An increase of exposure to environmental pollutants and sunlight are among the causative agents of the disease. Ursolic acid (UA), a well-known natural triterpenoid found in abundance in fruit peels, cranberries, and blueberries has been shown to possess beneficial health effects against a multitude of disorders including, cardiovascular, neurological, and oncological disorders. However, epigenetic modulation of UA in skin carcinogenesis is still poorly understood. Increasing evidence suggests epigenetics play an important role in the development and progression of cancer including NMSC. Among its many anti-cancer activities, UA has also been shown to have the ability to modulate epigenetic mechanisms in vitro and thus presents an attractive candidate to target the underlying epigenetic mechanisms of skin carcinogenesis. Preliminary data in our laboratory and that of others points to epigenetic regulation of key genes at the center of UA activities: 1) Skin carcinogenesis is enhanced in Nrf2 (-/-) mice; 2) The expression Nrf2 and its target gene HO-1 is reduced in skin tumors of Nrf2 (+/+) mice; 3) UA inhibits TPA-induced ear edema and tumor promotion; 4) Hypermethylation of the promoter region of Nrf2 resulting in reduced expression and its target genes is closely associated with prostate tumor progression; 5) Dietary phytochemicals epigenetically modify the hypermethylation of the Nrf2 promoter region and inhibit TPA-induced transformation. Based on the aforementioned observations, it was hypothesized UA can suppress skin carcinogenesis, in part, through the epigenetic regulation of Nrf2 signaling. We demonstrated for the first time that UA restores the expression of Nrf2 by demethylating CpG islands in the Nrf2 promoter in mouse epidermal cells resulting in an increase in the expression of cytoprotective detoxifying/antioxidant enzymes and suppression of tumor promoter-induced cell transformation. Furthermore, we demonstrate UA is able to suppress skin carcinogenesis in vivo using a relevant and novel B[a]P/TPA skin carcinogenesis model. The long-term goal of this research is to understand some of the underlying epigenetic mechanisms driving skin carcinogenesis and to develop safe and effective strategies to prevent/treat NMSC using phytochemicals such as UA who possess anti-cancer properties.
NotePh.D.
NoteIncludes bibliographical references
Noteby Christina N. Ramirez
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/t3-rrwe-p725
Languageeng
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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