Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

Abstract

BackgroundThere is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA.MethodsTo determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis.ResultsWe found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth.ConclusionWe conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype.

Effect of quinolinyl acrylate derivatives on prostate cancer in vitro and in vivo

“…Anchorage independent growth was assayed in cells grown in 0.6% agar followed by the procedure already described [11,17]. Briefly, PC-3 and LNCaP cells (1×10 5 ) were incubated with the compound A at its respective IC 50 or vehicle on a semi-solid agar layer for 14 days and the total number of colonies and the relative colony size cells were determined after staining the cells.…”

New 4-Maleamic Acid and 4-Maleamide Peptidyl Chalcones as Potential Multitarget Drugs for Human Prostate Cancer

“…To test for anchorage-independent growth, cells were grown in 0.6% agar (17). Briefly, one milliliter of a mixture of 1.2% Noble agar (Gibco-In Vitrogen, Karlsruhe, Germany) and RPMI medium (1:1) was added into each well of a six-well plate.…”

Colonic adenocarcinoma in a 13-year-old with cystic fibrosis

“…Increased cell turnover, abnormalities of bile absorption, chloramphenicol exposure, selenium deficiency, vitamin E malabsorption, and steatorrhea have all been proposed as possible factors that predispose patients to malignancy [7][8][9][10][11][12]. Bile acids may prevent colon cancer by promoting cell cycle arrest and apoptosis, and vitamin E is thought to help prevent colon malignancy by decreasing the Fig.…”

“…1 Inflammatory mass in the right pelvis and mild right-sided hydroureteronephrosis. formation of mutagens arising from free-radical oxidation of fecal lipids [10,11]. Selenium has been found to induce p53-mediated apoptosis and cell cycle arrest in colon cancer cells [13].…”