deoxycholic-acid and Ovarian-Neoplasms

Unique biologic activities have been identified for the 4 different bile acids: cholic acid (CA, chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and ursodeoxycholic acid (UDCA). The aim of this study was to examine and compare the effects of these 4 bile acids on the human ovarian cancer cell lines A2780 and A2780-CP-R(cisplatin-resistant) and to evaluate mechanisms of action.. Antiproliferative effects were determined by the cytotoxic MTT assay. Cells undergoing apoptosis were identified by morphologic analysis of cells stained using Diff-Quick and nuclear staining with DAPI and by quantitative nucleosome ELISA assay. Cells were lysed in buffer after 24 h of exposure to three different concentrations of bile acid (50 mM, 200 mM, and 400 mM) and protein concentrations were determined. Cell extracts containing 25 mg of protein were assayed for protein kinase C (PKC) enzyme activity.. None of the bile acids stimulated proliferation of ovarian cancer cells. CA and UDCA had only minimal cytotoxic effect even at maximum concentrations. In contrast, DCA and CDCA administration resulted in statistically significant dose-dependent cytotoxicity in both platinum sensitive and platinum-resistant cell lines (p<0.05). Cells incubated with DCA and CDCA exhibited morphologic features characteristic of apoptosis. The quantitative nucleosome ELISA assay demonstrated over 10 times increased nucleosome levels after cells were treated for 24 h by DCA and CDCA at 200 mM and 400 mM as compared to CA or UDCA treatment and to untreated controls (p<0.01). All 4 bile acids reduced PKC activity at concentrations of 200 and 400 mM (p<0.01).. CDCA and DCA have significant cytotoxic activity in ovarian cancer cells via induction of apoptosis. The mechanism of apoptosis appears to be mediated by alternative kinases distinct from PKC. CDCA and DCA may have clinical utility in the treatment of ovarian cancer pending in vivo confirmation of activity especially in cisplatin-resistant disease.

Topics: Antineoplastic Agents; Apoptosis; Bile Acids and Salts; Cell Line, Tumor; Cell Proliferation; Chenodeoxycholic Acid; Cholic Acid; Coloring Agents; Deoxycholic Acid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Nucleosomes; Ovarian Neoplasms; Protein Kinase C; Tetrazolium Salts; Thiazoles; Ursodeoxycholic Acid

Topics: Animals; Antibody Specificity; Antigens, Neoplasm; Chromatography, Gel; Cystadenocarcinoma; Deoxycholic Acid; Female; Fluorescent Antibody Technique; Humans; Immune Sera; Immunosorbent Techniques; Ovarian Neoplasms; Perchlorates; Potassium Chloride; Rabbits; Tissue Extracts

Inhibition of migration of leukocytes from patients with serous cystadenocarcinoma of the ovary was studied by the use of several different types of ovarian carcinoma extract as antigen. KCl extract of an ovarian carconoma was found to be the most effective antigen preparation in comparison with saline, deoxycholate, and perchloric acid extracts. Low concentrations of KCl ovarian carcinoma extract significantly inhibited migration of leukocytes from 11 of 17 patients with ovarian carcinoma (migration index, less than 0.74). Leukocytes from patients with breast, colon, or endometrial carcinoma showed minimal reactivity with ovarian carcinoma KCl extract, and leukocytes from patients with ovarian carcinoma showed minimal reactivity with KCl extracts of breast, colon, and endometrial carcinoma. These results suggested that the 3 M KCl procedure is superior for the isolation of antigens active in the leukocyte migration inhibition test and that this test may be of use for the isolation of tumor-associated antigen and the immunodiagnosis of ovarian carcinoma.

Topics: Antibody Specificity; Antigens, Neoplasm; Carcinoembryonic Antigen; Cell Migration Inhibition; Cystadenocarcinoma; Deoxycholic Acid; Female; Humans; Leukocytes; Neoplasms; Ovarian Neoplasms; Perchlorates; Potassium Chloride