Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence

  title={Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence},
  author={Sandeep Akare and Samira Jean-Louis and Wemin Chen and Daniel J. Wood and Ashley A. Powell and Jesse D. Martinez},
  journal={International Journal of Cancer},
Agents that can modulate colonic environment and control dysregulated signaling are being evaluated for their chemopreventive potential in colon cancer. Ursodeoxycholate (UDCA) has shown chemopreventive potential in preclinical and animal models of colon cancer, but the mechanism behind it remains unknown. Here biological effects of UDCA were examined to understand mechanism behind its chemoprevention in colon cancer. Our data suggests that UDCA can suppress growth in a wide variety of cancer… 

The chemopreventive agent ursodeoxycholic acid inhibits proliferation of colon carcinoma cells by suppressing c-Myc expression

Ursodeoxycholic acid (UDCA) can prevent chemical and colitis-associated colon carcinogenesis by unknown mechanism(s). One of the processes underlying the chemopreventive action could be the

Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth

It was found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells, and it was determined that UD CA suppressed levels of CDK2, CDK4, and CDK6.

Differential Regulation of EGFR–MAPK Signaling by Deoxycholic Acid (DCA) and Ursodeoxycholic Acid (UDCA) in Colon Cancer

This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancerdevelopment, with a particular emphasis on bile acid regulation of the EGFR–MAPK pathway.

UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation

It is shown that UDCA inhibits proliferation of nontransformed intestinal epithelial cells by inducing a sustained hyperphosphorylation of ERK1 kinase which slows down the cell cycle and reduces expression of Irs‐1 protein.

Cancer chemoprevention and nutriepigenetics: state of the art and future challenges.

The potential of natural chemopreventive agents to counteract cancer-related epigenetic alterations by influencing the activity or expression of DNA methyltransferases and histone modifying enzymes is summarized.

Ursodeoxycholic Acid but Not Tauroursodeoxycholic Acid Inhibits Proliferation and Differentiation of Human Subcutaneous Adipocytes

While TUDCA has neutral effect on human preadipocytes and adipocytes, the therapeutic use of UDCA different from treating cholestatic diseases should be considered with caution because UDCA alters functions of human adipose cells.

STK31 maintains the undifferentiated state of colon cancer cells.

It is reported that STK31 is robustly and heterogeneously expressed in colon cancer tissues and plays a critical role in determining the differentiation state of colon cancer cells.

Cancer Chemoprevention and Nutri-Epigenetics: State of the Art and Future Challenges

Evidence now indicates that epigenetic alterations contribute to major cellular defects, for example epigenetic silencing of detoxifying enzymes, tumor suppressor genes, cell cycle regulators, apoptosis-inducing and DNA repair genes, nuclear receptors, signal transducers and transcription factors by promoter methylation.

Cancer chemoprevention by targeting the epigenome.

A comprehensive overview of the current literature on chemopreventive agents and their influence on major epigenetic mechanisms, that is DNA methylation, histone acetylation andmethylation, and microRNAs, both in vitro and in rodent and human studies is given, taking into consideration specific mechanisms of action, target sites, concentrations, methods used for analysis, and outcome.

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

The current review will describe the latest achievements in using naturally produced compounds targeting epigenetic regulators and modulators of gene transcription in vitro and in vivo to generate novel anticancer therapeutics.



Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells.

The findings suggest that the inhibitory effect of UDCA in DCA-induced apoptosis is partly mediated by modulation of EGFR/Raf-1/ERK signaling.

Ursodeoxycholic Acid Can Suppress Deoxycholic Acid-Induced Apoptosis by Stimulating Akt/PKB-Dependent Survival Signaling

UDCA could suppress DCA-induced apoptosis in a time- and dose-dependent manner and that this effect correlated with Akt phosphorylation, suggesting that UDCA can protect HCT116 cells against DCA's apoptosis by stimulating Akt-dependent survival signaling.

Mechanism of Action of Chemoprotective Ursodeoxycholate in the Azoxymethane Model of Rat Colonic Carcinogenesis: Potential Roles of Protein Kinase C-α, -βII, and -ξ

The studies suggest that changes in specific isoforms of PKC (particularly, PKC-α, -βII, -δ, and/or -ξ) are involved in colonic malignant transformation in the AOM model but do not account for the chemopromotional actions of cholic acid in this model.

Sodium butyrate induces growth arrest and senescence‐like phenotypes in gynecologic cancer cells

The effect of NaB on senescence induction was not coupled with the predominance of hypophosphorylated pRb forms in the cervical cancer cells, suggesting that NaB had the potential to elicit SLPs through p21‐mediated withdrawal from cell cycle progression.

Different bile acids exhibit distinct biological effects: the tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation.

Results indicate that different bile acids exhibit distinct biological activities and suggest that the cytotoxicity reported for DCA may be due to its capacity to induce apoptosis via a protein kinase C-dependent signaling pathway.

Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms

A thiol reduction devoid of toxicity as that operated by NAC apparently leads to terminal differentiation of normal and cancer cells through a pleiade of converging mechanisms, many of which are targets of the recently developed differentiation therapy.

Bile acid hydrophobicity is correlated with induction of apoptosis and/or growth arrest in HCT116 cells.

It is found that the rapidity with which, and the degree to which, bile acids could induce apoptosis or growth arrest was correlated with their relative hydrophobicities, and that hydrophobicity is an important determinant of the biological activity exhibited bybile acids.