Potentiated antitumor effects of a combination therapy with a farnesyltransferase inhibitor L-744,832 and butyrate in vitro.
Farnesyltransferase inhibitors, butyrate and butyric acid derivatives have previously been reported to exert anti-tumor activity in experimental models in vitro and in vivo and have recently gained acceptance as potential anticancer agents. In our study, we examined antitumor effects of a combination of a farnesyltransferase inhibitor L-744,832 and butyrate in vitro against MDA-MB-231 and MIA PaCa-2 human cancer cells. This combination therapy showed synergistic antitumor activity against MDA-MB-231 cells, which was at least in part due to induction of p27KIP1 expression. Both drugs increased intracellular levels of p53 as well but there was no significant difference between the groups treated with single drugs and the group treated with their combination. In MIA PaCa-2 cells, the combination therapy exerted additive antitumor activity. Our results illustrate possible application of the farnesyltransferase inhibitor L-744,832 and butyrate as a combination therapy of cancer.
Kopec
Maciej
M
Department of Immunology, Centre of Biostructure Research, The Medical University of Warsaw, 02-004 Warsaw, Poland.
Strusinska
Katarzyna
K
Legat
Magdalena
M
Makowski
Marcin
M
Jakobisiak
Marek
M
Golab
Jakub
J
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002087:Butyrates / Q000494:pharmacology* / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004359:Drug Therapy, Combination; D051231:Farnesyltranstransferase; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D002087:Butyrates; D018797:Cell Cycle Proteins; C096898:L 744832; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008715:Methionine; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase