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Tauroursodeoxycholate inhibits human cholangiocarcinoma growth via Ca2+-, PKC-, and MAPK-dependent pathways.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2004 Jun; Vol. 286 (6), pp. G973-82. Date of Electronic Publication: 2003 Dec 30. - Publication Year :
- 2004
-
Abstract
- 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 Ca(2+) concentration ([Ca(2+)](i)) chelator, and H7, a PKC-alpha inhibitor. TUDCA increased [Ca(2+)](i) and membrane translocation of the Ca(2+)-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.
- Subjects :
- Biological Transport drug effects
Calcium metabolism
Cell Line, Tumor
Humans
Intracellular Membranes metabolism
Mitogen-Activated Protein Kinases metabolism
Osmolar Concentration
Phosphorylation
Protein Kinase C metabolism
Protein Kinase C-alpha
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-raf metabolism
Taurochenodeoxycholic Acid administration & dosage
Time Factors
Bile Duct Neoplasms metabolism
Bile Duct Neoplasms pathology
Bile Ducts, Intrahepatic
Cholangiocarcinoma metabolism
Cholangiocarcinoma pathology
Taurochenodeoxycholic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1857
- Volume :
- 286
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 14701718
- Full Text :
- https://doi.org/10.1152/ajpgi.00270.2003