Taurin-conjugated ursodeoxycholic acid has a reversible inhibitory effect on human keratinocyte growth

The effect of bile acids on adenosine 3',5'-cyclic monophosphate (cAMP) synthesis was investigated in isolated hamster hepatocytes. Bile acids had no direct effect on cAMP production. However, ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid inhibited, by approximately 45%, cAMP formation induced by concentrations of glucagon greater than 1 nM, with a respective half-maximum inhibitory effect observed at 4 +/- 2 microM. Similar inhibition was observed with phorbol 12-myristate 13-acetate (PMA). Chenodeoxycholic, murocholic, and taurodeoxycholic acids were the next most potent bile acids. Taurolithocholic acid was 100-fold less potent than UDCA, whereas both ursocholic and taurocholic acids had no effect at concentrations up to 0.5 mM. Neither bile acids nor PMA affected either the binding of glucagon to its receptor, the cAMP-dependent phosphodiesterase, adenylate cyclase, or the inhibitory and stimulatory (Gs) GTP-binding proteins. The inhibitory effect of PMA and UDCA on glucagon-induced cAMP synthesis was abolished in the presence of the protein kinase C (PKC) inhibitor, staurosporine. Furthermore, UDCA induced PKC translocation from cytosol to membrane and stimulated phosphorylation of an 80-kDa protein substrate for PKC. In conclusion, mediated by PKC activation, bile acids inhibit glucagon-induced cAMP synthesis by uncoupling the glucagon receptor and Gs.

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Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis

Cell Death Discovery ◽

10.1038/s41420-021-00589-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Huan Zhang ◽

Huanji Xu ◽

Chenliang Zhang ◽

Qiulin Tang ◽

Feng Bi

Keyword(s):

Colorectal Cancer ◽

Bile Acid ◽

Ursodeoxycholic Acid ◽

Bile Acids ◽

Inhibitory Effect ◽

Bile Acid Metabolism ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Rhoa Activity ◽

Relationship Of

AbstractThe Hippo/YAP pathway plays an important role in the development of cancers. Previous studies have reported that bile acids can activate YAP (Yes Associated Protein) to promote tumorigenesis and tumor progression. Ursodeoxycholic acid (UDCA) is a long-established old drug used for cholestasis treatment. So far, the effect of UDCA on YAP signaling in colorectal cancer (CRC) is not well defined. This study means to explore relationship of UDCA and YAP in CRC. UDCA suppressed YAP signaling by activating the membrane G-protein-coupled bile acid receptor (TGR5). TGR5 mainly regulated cAMP/PKA signaling pathway to inhibit RhoA activity, thereby suppressing YAP signaling. Moreover, the restoration of YAP expression alleviated the inhibitory effect of UDCA on CRC cell proliferation. In AOM/DSS-induced CRC model, UDCA inhibited tumor growth in a concentration-dependent manner and decreased expression of YAP and Ki67. UDCA plays a distinguished role in regulating YAP signaling and CRC growth from the primary bile acids and partial secondary bile acids, demonstrating the importance of maintaining normal intestinal bile acid metabolism in cancer patients. It also presents a potential therapeutic intervention for CRC.

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Inhibitory effect of ursodeoxycholic acid on rat liver microsomal bilirubin UDP-glucuronosyltransferase

Hepatology ◽

10.1016/0270-9139(94)90652-1 ◽

1994 ◽

Vol 19 (4) ◽

pp. I122

Author(s):

E SANCHEZPOZZI

Keyword(s):

Ursodeoxycholic Acid ◽

Rat Liver ◽

Inhibitory Effect ◽

Udp Glucuronosyltransferase

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The inhibitory effect of ursodeoxycholic acid and pentoxifylline on platelet derived growth factor-stimulated proliferation is distinct from an effect by cyclic AMP

Immunopharmacology ◽

10.1016/s0162-3109(98)00021-6 ◽

1998 ◽

Vol 39 (3) ◽

pp. 181-191 ◽

Cited By ~ 13

Author(s):

Theresa C. Peterson ◽

Gordon Slysz ◽

Richard Isbrucker

Keyword(s):

Growth Factor ◽

Cyclic Amp ◽

Ursodeoxycholic Acid ◽

Inhibitory Effect ◽

Platelet Derived Growth Factor

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Role of mitochondria in the differential action of sodium deoxycholate and ursodeoxycholic acid on rat duodenum

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0561 ◽

2020 ◽

pp. 1-8

Author(s):

Adriana Pérez ◽

María Angélica Rivoira ◽

Valeria Rodríguez ◽

Ana Marchionatti ◽

Nori Tolosa de Talamoni

Keyword(s):

Ursodeoxycholic Acid ◽

Mitochondrial Biogenesis ◽

Mitochondrial Dynamics ◽

Krebs Cycle ◽

Atp Synthesis ◽

Sodium Deoxycholate ◽

Inhibitory Effect ◽

Transport Chain ◽

Rat Duodenum ◽

Krebs Cycle Enzymes

Sodium deoxycholate (NaDOC) inhibits the intestinal Ca2+ absorption and ursodeoxycholic acid (UDCA) stimulates it. The aim of this study was to determine whether NaDOC and UDCA produce differential effects on the redox state of duodenal mitochondria altering the Krebs cycle and the electron transport chain (ETC) functioning, which could lead to perturbations in the mitochondrial dynamics and biogenesis. Rat intestinal mitochondria were isolated from untreated and treated animals with either NaDOC, UDCA, or both. Krebs cycle enzymes, ETC components, ATP synthase, and mitochondrial dynamics and biogenesis markers were determined. NaDOC decreased isocitrate dehydrogenase (ICDH) and malate dehydrogenase activities affecting the ETC and ATP synthesis. NaDOC also induced oxidative stress and increased the superoxide dismutase activity and impaired the mitochondrial biogenesis and functionality. UDCA increased the activities of ICDH and complex II of ETC. The combination of both bile acids conserved the functional activities of Krebs cycle enzymes, ETC components, oxidative phosphorylation, and mitochondrial biogenesis. In conclusion, the inhibitory effect of NaDOC on intestinal Ca2+ absorption is mediated by mitochondrial dysfunction, which is avoided by UDCA. The stimulatory effect of UDCA alone is associated with amelioration of mitochondrial functioning. This knowledge could improve treatment of diseases that affect the intestinal Ca2+ absorption.

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Inhibitory Effect of Ursodeoxycholic Acid on Clostridium difficile Germination Is Insufficient to Prevent Colitis: A Study in Hamsters and Humans

Frontiers in Microbiology ◽

10.3389/fmicb.2018.02849 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

Lola-Jade Palmieri ◽

Dominique Rainteau ◽

Harry Sokol ◽

Laurent Beaugerie ◽

Marie Dior ◽

...

Keyword(s):

Clostridium Difficile ◽

Ursodeoxycholic Acid ◽

Inhibitory Effect

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Inhibitory effect of glycolic acid on ultraviolet B-induced c-fos expression, AP-1 activation and p53–p21 response in a human keratinocyte cell line

Cancer Letters ◽

10.1016/s0304-3835(02)00283-5 ◽

2002 ◽

Vol 186 (2) ◽

pp. 125-135 ◽

Cited By ~ 25

Author(s):

Kwang Soo Ahn ◽

Ki Sook Park ◽

Kyung Mi Jung ◽

Hai Kwan Jung ◽

Sun Hee Lee ◽

...

Keyword(s):

Cell Line ◽

Glycolic Acid ◽

Inhibitory Effect ◽

Ultraviolet B ◽

Human Keratinocyte ◽

Human Keratinocyte Cell Line ◽

Keratinocyte Cell ◽

Fos Expression

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1197. Inhibitory Effect of Ursodeoxycholic Acid on Clostridioides difficile Growth

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1382 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S621-S621

Author(s):

Faris Alnezary ◽

M Jahangir Alam ◽

Masaad Almutairi ◽

Saad Fallatah ◽

Khurshida Begum ◽

...

Keyword(s):

Ursodeoxycholic Acid ◽

Galleria Mellonella ◽

Inhibitory Effect ◽

Secondary Bile Acid ◽

In Vivo Experiments ◽

Clostridioides Difficile ◽

Colony Forming Units ◽

Germination And Growth

Abstract Background Ursodeoxycholic acid (UDCA), a secondary bile acid, inhibits germination and growth of Clostridioides difficile in vitro, but the results from in vivo experiments have been conflicting. We evaluated the effects of UDCA on C. difficile in vitro and in a wax moth, Galleria mellonella model. Methods The in vitro growth and germination effects of UDCA on C. difficile were assessed with increased concentration of UDCA (0.001, 0.01, 0.05, and 0.1%). To assess treatment effects of UDCA, C. difficile spores (approximately 1x10^6-8 colony forming units (CFU)) were force fed to G. mellonella larvae treated with UDCA (50 mg/kg/day) 24 hours prior to C. difficile inoculation. Forty G. mellonella larvae were used for each experiment, which was repeated with two distinct strains (R20291 and CD196). Larvae were housed at 37°C and monitored for the next five days for mortality. Results In vitro experiment demonstrated inhibition of C. difficile growth at 0.1% concentration (P < 0.001 vs control). Larvae treated with UDCA had a numerically higher survival rate (60% / 24/40) compared to controls (40% / 16/40) but the results were not statistically significant (p=0.14). Identical rates of survival were observed in the control arms for both strains (40%) and similar in the treatment arms (R20291: 70%; CD 196: 50%). Conclusion Overall, UDCA shows inhibitory effect of growth and germination of C. difficile in vitro. However, in our G. mellonella model, a single dose of UDCA given prior to infection did not prevent CDI. Further dose dependent, and multiday studies investigating the role of UDCA in CDI is needed to better understand this in vitro / in vivo paradox. Disclosures Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)

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