The effect of clotrimazole on energy substrate uptake and carcinogenesis in intestinal epithelial cells

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Gonçalves P (Author) FMUP; Gregorio, I (Author) Other; Araújo JR (Author) FMUP; Martel, F (Author) FMUP

Journal

Title: Anti-Cancer Drugs

Vol. 23

Pages: 220-229

ISSN: 0959-4973

Publisher: Wolters Kluwer Health

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-002-DQF

DOI: 10.1097/cad.0b013e32834d9ad2

Abstract (EN): Clotrimazole has anticarcinogenic activity in several cell types. Our aims were to investigate the anticarcinogenic effect of clotrimazole in a tumoral intestinal epithelial (Caco-2) cell line, to compare it with the effect in a nontumoral intestinal epithelial cell line (IEC-6 cells), and to investigate inhibition of energy substrate uptake as a mechanism contributing to it. The effect of clotrimazole on cell proliferation, viability and differentiation, (3)H-deoxyglucose ((3)H-DG), (3)H-O-methyl-glucose ((3)H-OMG), and (14)C-butyrate uptake, as well as mRNA expression levels of glucose transporters was assessed. In Caco-2 cells, clotrimazole decreased cellular viability and proliferation and increased cell differentiation. The effect on cell proliferation and viability was potentiated by rhodamine123. Clotrimazole also decreased cellular viability and proliferation in IEC-6 cells, but increased the cellular DNA synthesis rate and had no effect on cell differentiation. Exposure of Caco-2 cells to clotrimazole (10 mu mol/l) for 1 and 7 days increased (by 20-30%) the uptake of (3)H-DG and (3)H-OMG, respectively, but had no effect on (14)C-butyrate uptake. The effect on (3)H-DG and (3)H-OMG transport was maximal at 10 mu mol/l, and the pharmacological characteristics of transport were not changed. However, clotrimazole changed the mRNA expression levels of the facilitative glucose transporter 2 and the Na(+)-dependent glucose cotransporter. Clotrimazole exhibits comparable cytotoxic effects in tumoral and nontumoral intestinal epithelial cell lines. In Caco-2 cells, the cytotoxic effect of clotrimazole was strongly potentiated by the inhibition of oxidative phosphorylation. Moreover, stimulation of glucose uptake might be a compensation mechanism in response to the glycolysis inhibition caused by clotrimazole. Anti-Cancer Drugs 23: 220-229 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10