title: Anti-invasive effects and proapoptotic activity induction by the rexinoid IIF and valproic acid in combination on colon cancer cell lines.
abstract: In this study, we investigated the antiproliferative and anti-invasive mechanism action of sodium valproate (VPA), an inhibitor of histone deacetylase (HDAC) activity, in combination with the rexinoid 6-OH-11-O-hydroxyphenanthrene (IIF), a ligand of retinoid X receptor (RXR), in the HT-29 and LoVo colon cancer cell lines. VPA inhibited HDAC-1 and increased RXRγ expression. VPA and IIF reduced viability in a dose- and time-dependent manner. The combined use of VPA and IIF enhanced the apoptosis induction. In particular, the BCL2 level decreased, while levels of BAX, cleaved caspase-3 and caspase-9 increased. The same treatment also reduced invasiveness of HT-29 cell line through the inhibition of metalloproteinase-9 (MMP9) expression, and MMP9 and MMP2 activity, with an increase of tissue inhibitors of MMPs TIMP1 and TIMP2. In conclusion, VPA and IIF have strong proapoptotic and anti-invasive effects in the HT-29 colon cancer cell line and their effects are enhanced when used together.
authors: Department of Experimental Evolutive Biology, University of Bologna, Bologna, Italy.
authors: A
authors: A
authors: Papi
authors: A M
authors: AM
authors: Ferreri
authors: F
authors: F
authors: Guerra
authors: M
authors: M
authors: Orlandi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D047491:Retinoid X Receptor gamma / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives; D014635:Valproic Acid / Q000008:administration & dosage; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D056572:Histone Deacetylase Inhibitors; C475805:IIF compound; D047491:Retinoid X Receptor gamma; D051028:bcl-2-Associated X Protein; D014212:Tretinoin; D014635:Valproic Acid; D053148:Caspase 3; D053453:Caspase 9; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9