RXRgamma and PPARgamma ligands in combination to inhibit proliferation and invasiveness in colon cancer cells.
Nuclear retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs are potential candidates as drug target for cancer prevention and treatment. We investigated if the rexinoid 6-OH-11-O-hydroxyphenantrene (IIF) potentiates the antitumoral properties of PPARgamma ligands as ciglitazone and pioglitazone, on two colon cancer cell lines: HCA-7 and HCT-116. Drugs inhibited cell growth and induced apoptosis synergistically. The combination resulted in a decrease of cyclooxigenase-2, metalloproteinases-2 and -9 expression level and activity while PPARgamma, RXRgamma and tissue inhibitors of metalloproteinase-1 and -2 expression were increased. Finally, IIF potentiated PPAR transcriptional activity by enhancement of peroxisome proliferator response elements transactivation.
Papi
Alessio
A
Department of Experimental Evolutionary Biology, University of Bologna, Italy. alessio.papi2@unibo.it
Rocchi
Paola
P
Ferreri
Anna Maria
AM
Orlandi
Marina
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D045325:HCT116 Cells; D006801:Humans; D008024:Ligands; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D020218:Response Elements / Q000187:drug effects; D047491:Retinoid X Receptor gamma / Q000819:agonists* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology
C475805:IIF compound; D008024:Ligands; D047495:PPAR gamma; D047491:Retinoid X Receptor gamma; D045162:Thiazolidinediones; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014212:Tretinoin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C039671:ciglitazone; D000077205:Pioglitazone