Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 286, Issue 6, Pages G973-G982Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00270.2003
Keywords
bile acids; bile ducts; cyclic adenosine monophosphate; cancer; mitosis
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Funding
- NIDDK NIH HHS [DK-58411, DK-54208] Funding Source: Medline
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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-alpha inhibitor. TUDCA increased [Ca2+](i) and membrane translocation of the Ca2+-dependent PKC-alpha 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-alpha but independent from Raf proteins and MAPK p38 and JNK/ stress-activated protein kinases. TUDCA may be important for the treatment of cholangiocarcinoma.
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