HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/G973    most recent 00270.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Alpini, G. Articles by LeSage, G. Search for Related Content PubMed PubMed Citation Articles by Alpini, G. Articles by LeSage, G.

LIVER AND BILIARY TRACT

Tauroursodeoxycholate inhibits human cholangiocarcinoma growth via Ca²⁺-, PKC-, and MAPK-dependent pathways

¹ Internal Medicine and ²Medical Physiology and ³Division of Research and Education, Scott & White Hospital and The Texas A&M University System Health Science Center, College of Medicine, and ⁴Central Texas Veterans Health Care System, Temple, Texas 76504

Submitted 24 June 2003 ; accepted in final form 26 December 2003

Tauroursodeoxychate (TUDCA) is used for the treatment of cholangiopathies including primary sclerosing cholangitis, which is considered the primary risk factor for cholangiocarcinoma. The effect of TUDCA on cholangiocarcinoma growth is unknown. We evaluated the role of TUDCA in the regulation of growth of the cholangiocarcinoma cell line Mz-ChA-1. TUDCA inhibited the growth of Mz-ChA-1 cells in concentration- and time-dependent manners. TUDCA inhibition of cholangiocarcinoma growth was blocked by BAPTA-AM, an intracellular Ca²⁺ concentration ([Ca²⁺]_i) chelator, and H7, a PKC- inhibitor. TUDCA increased [Ca²⁺]_i and membrane translocation of the Ca²⁺-dependent PKC- in Mz-ChA-1 cells. TUDCA inhibited the activity of MAPK, and this inhibitory effect of TUDCA was abrogated by BAPTA-AM and H7. TUDCA did not alter the activity of Raf-1 and B-Raf and the phosphorylation of MAPK p38 and JNK/stress-activated protein kinase. TUDCA inhibits Mz-ChA-1 growth through a signal-transduction pathway involving MAPK p42/44 and PKC- but independent from Raf proteins and MAPK p38 and JNK/stress-activated protein kinases. TUDCA may be important for the treatment of cholangiocarcinoma.

bile acids; bile ducts; cyclic adenosine monophosphate; cancer; mitosis

This article has been cited by other articles:

				H. Francis, P. Onori, E. Gaudio, A. Franchitto, S. DeMorrow, J. Venter, S. Kopriva, G. Carpino, R. Mancinelli, M. White, et al. H3 Histamine Receptor-Mediated Activation of Protein Kinase C{alpha} Inhibits the Growth of Cholangiocarcinoma In vitro and In vivo Mol. Cancer Res., October 1, 2009; 7(10): 1704 - 1713. [Abstract] [Full Text] [PDF]

				S. DeMorrow, H. Francis, E. Gaudio, J. Venter, A. Franchitto, S. Kopriva, P. Onori, R. Mancinelli, G. Frampton, M. Coufal, et al. The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway Am J Physiol Gastrointest Liver Physiol, December 1, 2008; 295(6): G1150 - G1158. [Abstract] [Full Text] [PDF]

				J. Kanchanapoo, M. Ao, R. Prasad, C. Moore, C. Kay, P. Piyachaturawat, and M. C. Rao Role of protein kinase C-{delta} in the age-dependent secretagogue action of bile acids in mammalian colon Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1851 - C1861. [Abstract] [Full Text] [PDF]