10(9)-hydroxystearic-acid and Adenocarcinoma

Histone deacetylases, HDACs, have been demonstrated to play a critical role in epigenetic signaling and were found to be overexpressed in several type of cancers; therefore, they represent valuable targets for anticancer therapy. 9-Hydroxystearic acid has been shown to bind the catalytic site of HDAC1, inducing G0/G1 phase cell cycle arrest and activation of the p21

Topics: Adenocarcinoma; Albumins; Cell Membrane; Cell Proliferation; Cell Survival; Chemistry Techniques, Synthetic; Colonic Neoplasms; Drug Discovery; HCT116 Cells; Histone Deacetylase 1; HT29 Cells; Humans; Keratins; Nanoparticles; Reactive Oxygen Species; S Phase Cell Cycle Checkpoints; Signal Transduction; Solubility; Stearic Acids

The epidermal growth factor has long been known to be strictly correlated with the highly proliferating activities of cancer cells and primary tumors. Moreover, in the nucleus, the epidermal growth factor/epidermal growth factor receptor complex (EGF/EGFR) functions as a transcriptional regulator that activates the cyclin D1 gene. 9-hydroxystearic acid (9-HSA) induces cell proliferation arrest and differentiation in HT29 colon cancer cells by inhibiting histone deacetylase 1 (HDAC1). 9-HSA-treated HT29, when stimulated with EGF, are not responsive and surprisingly undergo a further arrest. In order to understand the mechanisms of this effect, we analyzed the degree of internalization of the EGF/EGFR complex and its interactions with HDAC1. It appears that HDAC1, as modified by 9-HSA, is unable to associate with cyclin D1, interfering with the cell proliferation program, and sequesters the EGF/EGFR complex interrupting the transduction of the mitogenic signal.

Topics: Adenocarcinoma; Cell Proliferation; Colonic Neoplasms; Cyclin D1; Epidermal Growth Factor; ErbB Receptors; Fluorescent Antibody Technique; Histone Deacetylase 1; Histone Deacetylases; HT29 Cells; Humans; Signal Transduction; Stearic Acids

The in vitro effects of hydroxystearic acid on the proliferation of human colon carcinoma cells (HT29) and human embryonic intestine cells (I407) were examined and compared to previous results obtained in murine C108 lung carcinoma cells. The cells were cultured in the presence, or in the absence, of hydroxystearic acid and tested for cell proliferation and viability; the distribution of cells in the cell cycle was evaluated by flow cytometry. Results show that hydroxystearic acid is also an inhibitor of human cell proliferation, and not only of murine C108 cells. Differently from C108 cells, which upon treatment with hydroxystearic acid accumulate in G2-M phases, hydroxystearic acid-treated HT29 cells increase significantly in numbers in G0-G1; I407, embryonic cells used as a control, when treated show only a slight increase in G0-G1.

Topics: Adenocarcinoma; Animals; Cell Cycle; Cell Division; Cells, Cultured; Colonic Neoplasms; Depression, Chemical; Humans; Intestines; Lung Neoplasms; Mice; Stearic Acids; Tumor Cells, Cultured