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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Expression of transporters potentially involved in the targeting of cytostatic bile acid derivatives to colon cancer and polyps.

Drug targeting might help to overcome resistance to chemotherapy. Here we investigated whether colon cancer and polyps do express functional carriers involved in the uptake of cytostatic bile acid derivatives, in this case Bamet-UD2 [cis-diammine-bisursodeoxycholate-platinum(II)], which has been reported to be taken up by colon cancer cells "in vitro", efficiently induce apoptosis and overcome resistance to cisplatin. Although at lower levels than in ileum, a detectable expression of ASBT, OATP8/1B3, OCT1 and OSTalpha in colon tissue was found, which was not impaired in colon cancer or polyps. The expression of OATP-A/1A2 and OSTbeta was also found in colon, but this was markedly decreased in neoplastic colon tissue. In contrast, the expression of OATP-C/1B1 was low in colon but significantly enhanced in neoplastic colon tissue. MDR1 and MRP2 were poorly expressed in colon as compared with ileum, whereas MRP3 expression was higher in colon than in ileum. The abundance of mRNA for these ABC proteins was not changed in colon cancer or polyps. When RNA from different tissues was injected to Xenopus laevis oocytes their ability to take up taurocholate and Bamet-UD2 was enhanced (healthy ileum>healthy colon approximately neoplastic colon tissue). In all cases, uptake was lower for taurocholate than for Bamet-UD2, probably due to that ASBT mediates sodium-dependent uptake of both substrates, whereas additional transporters expressed in these tissues can participate in Bamet-UD2 uptake. In conclusion, our results suggest that the use of cytostatic bile acid derivatives might be a good pharmacological strategy for the treatment of colon tumors.[1]


  1. Expression of transporters potentially involved in the targeting of cytostatic bile acid derivatives to colon cancer and polyps. Ballestero, M.R., Monte, M.J., Briz, O., Jimenez, F., Gonzalez-San Martin, F., Marin, J.J. Biochem. Pharmacol. (2006) [Pubmed]
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