Record Details

An epigenetic perspective on pharmacologic ascorbate in colon cancer

ScholarsArchive at Oregon State University

Field Value
Title An epigenetic perspective on pharmacologic ascorbate in colon cancer
Names Kaiser, Matthew Carl (creator)
Rajendran, Praveen (creator)
Dashwood, Mohaiza W. (creator)
Levine, Mark A. (creator)
Michels, Alexander (creator)
Frei, Balz (creator)
Dashwood, Roderick H. (creator)
Date Issued 2013-04-18 (iso8601)
Note Honors Bachelor of Science (HBS)
Abstract Aim: There is growing interest in pharmacologic ascorbate (Asc) and its therapeutic properties (Levine et al. Adv Nutr 2011;2:78). W e examined cell viability, histone deacetylase (HDAC) expression, and related protein modifications in cancer versus non- cancer colon epithelial cells following exposure to Asc.
Methods: MTT assays were conducted in HCT116 colon cancer and CCD841 non-transformed colonic epithelial cells treated with 0.25 to 16 mM Asc or ascorbate-2-phosphate (AAp), in the presence and absence of catalase (CAT, 280 U/mg), or with 5 to 160 μM H₂O₂. Cell lysates obtained 6 h and 24 h post-treatment were immunoblotted as reported by Rajendran et al. Mol Cancer 2011;10:68.
Results: In MTT assays, IC₅₀ data were as follows: 8 mM Asc (CCD841); 3 mM Asc (HCT116), >50mM AAp (HCT116), and 65 μM H₂O₂ (HCT116). CAT protected against both Asc- and H₂O₂- induced cytotoxicity. At 6 h, Asc and H₂O₂ altered the expression of HDACs (HDAC4, HDAC6, SIRT3) and enhanced the acetylation of histone (H3, H4) and non-histone proteins (tubulin, p53).
Conclusions: Asc was more cytotoxic to colon cancer cells than non-cancer cells. Findings with the non-H₂O₂ producing compound AAp, and with CAT, implicated H₂O₂ in Asc-induced cytotoxicity. Asc was shown, for the first time, to alter epigenetic end-points related to HDAC changes in colon cancer cells.
Genre Video
Topic Kaiser
Identifier http://hdl.handle.net/1957/55927

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