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An epigenetic perspective on pharmacologic ascorbate in colon cancer
Author(s) -
Kaiser Matthew Carl,
Rajendran Praveen,
Dashwood Mohaiza W,
Levine Mark A,
Michaels Alexander,
Frei Balz,
Dashwood Roderick H
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.248.3
Subject(s) - cytotoxicity , acetylation , colorectal cancer , mtt assay , epigenetics , cancer cell , cytotoxic t cell , cancer research , microbiology and biotechnology , viability assay , histone deacetylase , chemistry , cancer , histone , apoptosis , medicine , biology , biochemistry , in vitro , gene
Aim There is growing interest in pharmacologic ascorbate (Asc) and its therapeutic properties (Levine et al. Adv Nutr 2011;2:78). We examined cell viability, histone deacetylase (HDAC) expression, and related protein modifications in cancer versus noncancer 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 H 2 O 2 . 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, IC 50 data were as follows: 8 mM Asc (CCD841); 3 mM Asc (HCT116), >;50mM AAp (HCT116), and 65 μM H 2 O 2 (HCT116). CAT protected against both Asc‐ and H 2 O 2 ‐ induced cytotoxicity. At 6 h, Asc and H 2 O 2 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‐H 2 O 2 producing compound AAp, and with CAT, implicated H 2 O 2 in Asc‐induced cytotoxicity. Asc was shown, for the first time, to alter epigenetic end‐points related to HDAC changes in colon cancer cells. Grant Funding Source : CA090890 , CA090890 , AT002034