An epigenetic perspective on pharmacologic ascorbate in colon cancer Conference Paper uri icon

abstract

  • AimThere 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.MethodsMTT assays were conducted in HCT116 colon cancer and CCD841 nontransformed colonic epithelial cells treated with 0.25 to 16 mM Asc or ascorbate2phosphate (AAp), in the presence and absence of catalase (CAT, 280 U/mg), or with 5 to 160 M H2O2. Cell lysates obtained 6 h and 24 h posttreatment were immunoblotted as reported by Rajendran et al. Mol Cancer 2011;10:68.ResultsIn MTT assays, IC50 data were as follows: 8 mM Asc (CCD841); 3 mM Asc (HCT116), >;50mM AAp (HCT116), and 65 M 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 nonhistone proteins (tubulin, p53).ConclusionsAsc was more cytotoxic to colon cancer cells than noncancer cells. Findings with the nonH2O2 producing compound AAp, and with CAT, implicated H2O2 in Ascinduced cytotoxicity. Asc was shown, for the first time, to alter epigenetic endpoints related to HDAC changes in colon cancer cells.Grant Funding Source: CA090890, CA090890, AT002034

published proceedings

  • FASEB JOURNAL

author list (cited authors)

  • Kaiser, M. C., Rajendran, P., Dashwood, M. W., Levine, M. A., Michaels, A., Frei, B., & Dashwood, R. H.

citation count

  • 0

complete list of authors

  • Kaiser, Matthew Carl||Rajendran, Praveen||Dashwood, Mohaiza W||Levine, Mark A||Michaels, Alexander||Frei, Balz||Dashwood, Roderick H

publication date

  • April 2013

publisher