Different bile acids exhibit distinct biological effects

The tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation

Jesse D Martinez, Elias D. Stratagoules, Janna M. LaRue, Ashley A. Powell, Paul R. Gause, Mary T. Craven, Claire M. Payne, Marianne B. Powell, Eugene W. Gerner, David L. Earnest

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Epidemiological studies have suggested that the concentration and composition of fecal bile acids are important determining factors in the etiology of colon cancer. However, the mechanism by which these compounds influence tumor development is not understood. To begin to elucidate their mechanism of action, four bile acids, cholic acid, chenodeoxycholic acid, deoxycholic acid (DCA), and ursodeoxycholic acid, were examined for their effects on the growth of several different tumor cell lines. We found that incubating cells with chenodeoxycholic acid or DCA caused morphological changes, seen by electron and light microscopy, that were characteristic of apoptosis, whereas incubating cells with ursodeoxycholic acid inhibited cell proliferation but did not induce apoptosis. Cholic acid had no discernible effect on cells. Notably, the apoptosis induced by DCA could be suppressed by inhibiting protein kinase C activity with calphostin C. These 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.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalNutrition and Cancer
Volume31
Issue number2
StatePublished - 1998

Fingerprint

ursodeoxycholic acid
deoxycholic acid
Ursodeoxycholic Acid
Deoxycholic Acid
bile acids
Bile Acids and Salts
Carcinogens
cell proliferation
apoptosis
promoter regions
Cell Proliferation
chenodeoxycholic acid
Apoptosis
cholic acid
Chenodeoxycholic Acid
Cholic Acid
neoplasms
protein kinase C
Protein Kinase C
feces composition

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Food Science

Cite this

Different bile acids exhibit distinct biological effects : The tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation. / Martinez, Jesse D; Stratagoules, Elias D.; LaRue, Janna M.; Powell, Ashley A.; Gause, Paul R.; Craven, Mary T.; Payne, Claire M.; Powell, Marianne B.; Gerner, Eugene W.; Earnest, David L.

In: Nutrition and Cancer, Vol. 31, No. 2, 1998, p. 111-118.

Research output: Contribution to journalArticle

Martinez, JD, Stratagoules, ED, LaRue, JM, Powell, AA, Gause, PR, Craven, MT, Payne, CM, Powell, MB, Gerner, EW & Earnest, DL 1998, 'Different bile acids exhibit distinct biological effects: The tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation', Nutrition and Cancer, vol. 31, no. 2, pp. 111-118.
Martinez, Jesse D ; Stratagoules, Elias D. ; LaRue, Janna M. ; Powell, Ashley A. ; Gause, Paul R. ; Craven, Mary T. ; Payne, Claire M. ; Powell, Marianne B. ; Gerner, Eugene W. ; Earnest, David L. / Different bile acids exhibit distinct biological effects : The tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation. In: Nutrition and Cancer. 1998 ; Vol. 31, No. 2. pp. 111-118.
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abstract = "Epidemiological studies have suggested that the concentration and composition of fecal bile acids are important determining factors in the etiology of colon cancer. However, the mechanism by which these compounds influence tumor development is not understood. To begin to elucidate their mechanism of action, four bile acids, cholic acid, chenodeoxycholic acid, deoxycholic acid (DCA), and ursodeoxycholic acid, were examined for their effects on the growth of several different tumor cell lines. We found that incubating cells with chenodeoxycholic acid or DCA caused morphological changes, seen by electron and light microscopy, that were characteristic of apoptosis, whereas incubating cells with ursodeoxycholic acid inhibited cell proliferation but did not induce apoptosis. Cholic acid had no discernible effect on cells. Notably, the apoptosis induced by DCA could be suppressed by inhibiting protein kinase C activity with calphostin C. These 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.",
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