Citeable URL: http://ir.library.oregonstate.edu/concern/articles/37720f51r

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Attribute Name	Values
Creator	Fischer, Kay A. Rajendran, Praveen Dashwood, Roderick H. Dashwood, Wan-Mohaiza Yamamoto, Masayuki Johnson, Gavin Li, Li Kim, Eunah Kang, Yuki Ho, Emily Löhr, Christiane V. Williams, David E. Lieberman, David A.
Abstract or Summary	Background: The dietary agent sulforaphane (SFN) has been reported to induce nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2)-dependent pathways as well as inhibiting histone deacetylase (HDAC) activity. The current investigation sought to examine the relationships between Nrf2 status and HDAC expression in preclinical and translational studies. Results: Wild type (WT) and Nrf2-deficient (Nrf2 ⁻/⁺ ) mice were treated with the colon carcinogen 1,2-dimethylhydrazine (DMH) followed by 400 ppm SFN in the diet (n = 35 mice/group). WT mice were more susceptible than Nrf2 ⁻/⁺ mice to tumor induction in the colon. Tumors from WT mice had higher HDAC levels globally and locally on genes such as cyclin-dependant kinase inhibitor 2a (Cdkn2a/p16) that were dysregulated during tumor development. The average tumor burden was reduced by SFN from 62.7 to 26.0 mm³ in WT mice and from 14.6 to 11.7 mm³ in Nrf2 ⁻/⁺ mice. The decreased antitumor activity of SFN in Nrf2 ⁻/⁺ mice coincided with attenuated Cdkn2a promoter interactions involving HDAC3. HDAC3 knockdown in human colon cancer cells recapitulated the effects of SFN on p16 induction. Human subjects given a broccoli sprout extract supplement (200 μmol SFN equivalents), or reporting more than five cruciferous vegetable servings per week, had increased p16 expression that was inversely associated with HDAC3 in circulating peripheral blood mononuclear cells (PBMCs) and in biopsies obtained during screening colonoscopy. Conclusions: Nrf2 expression varies widely in both normal human colon and human colon cancers and likely contributes to the overall rate of tumor growth in the large intestine. It remains to be determined whether this influences global HDAC protein expression levels, as well as local HDAC interactions on genes dysregulated during human colon tumor development. If corroborated in future studies, Nrf2 status might serve as a biomarker of HDAC inhibitor efficacy in clinical trials using single agent or combination modalities to slow, halt, or regress the progression to later stages of solid tumors and hematological malignancies.
Resource Type	Article
DOI	10.1186/s13148-015-0132-y
Date Available	2015-10-12T20:07:30+00:00
Date Issued	2015-09-18
Citation	Rajendran, P., Dashwood, W. M., Li, L., Kang, Y., Kim, E., Johnson, G., ... & Dashwood, R. H. (2015). Nrf2 status affects tumor growth, HDAC3 gene promoter associations, and the response to sulforaphane in the colon. Clinical Epigenetics, 7, 102. doi:10.1186/s13148-015-0132-y
Series	Clinical Epigenetic Vol. 7
Keyword	Nrf2 Sulforaphane HDAC3 Colon cancer p16 Broccoli
Rights Statement	In Copyright
Funding Statement (additional comments about funding)	This work is supported by a grant CA090890 from the National Cancer Institute, P30 grants ES00210 and ES02351 from the National Institute of Environmental Health Sciences, and by a Chancellor's Research Initiative from Texas A&M University. The open access publishing fees for this article have been covered by the Texas A&M University Online Access to Knowledge (OAK) Fund, supported by the University Libraries and the Office of the Vice President for Research.
Publisher	BioMed Central
Peer Reviewed	Yes
Language	English [eng]
Replaces	http://hdl.handle.net/1957/57513
Additional Information	description.provenance : Made available in DSpace on 2015-10-12T20:07:30Z (GMT). No. of bitstreams: 5 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) KangYukiLinusPaulingInstitNrf2StatusAffects.pdf: 2374744 bytes, checksum: bc82fbbb9279cf9c99bb4a108769d57e (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsFigureS1.pptx: 282613 bytes, checksum: 369e645f66adc31583c38c96e205399c (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsTableS1.pdf: 42814 bytes, checksum: 1ed9da063cf4694245474c2b490a784e (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsTableS2.pdf: 65730 bytes, checksum: f02cd353bf21d56ff23836e9883b27a3 (MD5) Previous issue date: 2015-09-18 description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-10-12T20:07:30Z (GMT) No. of bitstreams: 5 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) KangYukiLinusPaulingInstitNrf2StatusAffects.pdf: 2374744 bytes, checksum: bc82fbbb9279cf9c99bb4a108769d57e (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsFigureS1.pptx: 282613 bytes, checksum: 369e645f66adc31583c38c96e205399c (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsTableS1.pdf: 42814 bytes, checksum: 1ed9da063cf4694245474c2b490a784e (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsTableS2.pdf: 65730 bytes, checksum: f02cd353bf21d56ff23836e9883b27a3 (MD5) description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2015-10-12T20:06:17Z No. of bitstreams: 5 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) KangYukiLinusPaulingInstitNrf2StatusAffects.pdf: 2374744 bytes, checksum: bc82fbbb9279cf9c99bb4a108769d57e (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsFigureS1.pptx: 282613 bytes, checksum: 369e645f66adc31583c38c96e205399c (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsTableS1.pdf: 42814 bytes, checksum: 1ed9da063cf4694245474c2b490a784e (MD5) KangYukiLinusPaulingInstitNrf2StatusAffectsTableS2.pdf: 65730 bytes, checksum: f02cd353bf21d56ff23836e9883b27a3 (MD5)

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