Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation

被引：78

作者：

Milovic, V ^{[1
]}

Teller, IC ^{[1
]}

Faust, D ^{[1
]}

Caspary, WF ^{[1
]}

Stein, J ^{[1
]}

机构：

[1] Univ Frankfurt, Dept Med 2, D-60590 Frankfurt, Germany

来源：

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION | 2002年 / 32卷 / 01期

关键词：

bile salts; cell culture; colon cancer; epithelial cell proliferation; protein kinase C;

D O I：

10.1046/j.0014-2972.2001.00938.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Deoxycholic acid has long been attributed as a tumour promoter in the colon. It exerts its growth-related actions in a phorbol ester-like manner, by stimulating protein kinase C. The aim of this study was to investigate the effect of deoxycholic acid on proliferation and apoptosis in the colon, by exposing colon cancer cells to it in increasing concentrations. Methods Human colon cancer cells (Caco-2 and HT-29) were treated with deoxycholate or its two structural isomers, 3-beta-12-alpha-dihydroxy-5-beta-cholan-24-oic acid and 3-alpha- 12-beta-dihydroxy-5-beta-cholan-24-oic acid. Proliferation was evaluated by cell counting, and apoptosis by estimating percentage cell survival and assessment of nuclear morphology. Results Within the concentration range of up to 20 muM, deoxycholate stimulated growth of both human colon cancer cell lines. Its growth-promoting effect was abolished after inhibition of protein kinase C. At concentrations above 100 muM, deoxycholate induced apoptosis in both cell lines. Epimers of deoxycholate were significantly less potent in stimulating growth. Conclusion Low-dose deoxycholate stimulates colon cancer cell proliferation while > 100 mumol L-1 of this secondary bile acid induces apoptosis in colon cancer cells. Deoxycholate might promote the likelihood of malignant transformation by increasing epithelial cell turnover in the colon.

引用

页码：29 / 34

页数：6

共 34 条

[1] Protein kinase C α modulates growth and differentiation in Caco-2 cells [J].

Abraham, C ;

Scaglione-Sewell, B ;

Skarosi, SF ;

Qin, WY ;

Bissonnette, M ;

Brasitus, TA .

GASTROENTEROLOGY, 1998, 114 (03) :503-509

[2] CAMP-MEDIATED SIGNALS AS DETERMINANTS FOR APOPTOSIS IN PRIMARY GRANULOSA-CELLS [J].

AHARONI, D ;

DANTES, A ;

OREN, M ;

AMSTERDAM, A .

EXPERIMENTAL CELL RESEARCH, 1995, 218 (01) :271-282

[3]

BARTRAM HP, 1993, CANCER RES, V53, P3283

[4]

BARTRAM HP, 1991, CANCER RES, V51, P4238

[5]

Batta AK, 1998, CANCER RES, V58, P1684

[6] REGULATION OF PROTEIN-KINASE-C AND ROLE IN CANCER BIOLOGY [J].

BLOBE, GC ;

OBEID, LM ;

HANNUN, YA .

CANCER AND METASTASIS REVIEWS, 1994, 13 (3-4) :411-431

[7]

CRAVEN PA, 1986, CANCER RES, V46, P5754

[8] ROLE OF ACTIVATION OF PROTEIN-KINASE-C IN THE STIMULATION OF COLONIC EPITHELIAL PROLIFERATION AND REACTIVE OXYGEN FORMATION BY BILE-ACIDS [J].

CRAVEN, PA ;

PFANSTIEL, J ;

DERUBERTIS, FR .

JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (02) :532-541

[9]

Engle MJ, 1998, J CELL PHYSIOL, V174, P362, DOI 10.1002/(SICI)1097-4652(199803)174:3<362::AID-JCP10>3.0.CO

[10]

2-B

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