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	A Papi, A M Ferreri, F Guerra, M Orlandi
Journal	Anticancer research (Anticancer Res) Vol. 32 Issue 7 Pg. 2855-62 (Jul 2012) ISSN: 1791-7530 [Electronic] Greece
PMID	22753748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BAX protein, human Histone Deacetylase Inhibitors IIF compound Retinoid X Receptor gamma bcl-2-Associated X Protein Tretinoin Valproic Acid Caspase 3 Caspase 9 MMP2 protein, human Matrix Metalloproteinase 2 Matrix Metalloproteinase 9
Topics	Antineoplastic Combined Chemotherapy Protocols (pharmacology) Apoptosis (drug effects) Caspase 3 (metabolism) Caspase 9 (metabolism) Colonic Neoplasms (drug therapy, pathology) Dose-Response Relationship, Drug HT29 Cells Histone Deacetylase Inhibitors (administration & dosage) Humans Matrix Metalloproteinase 2 (metabolism) Matrix Metalloproteinase 9 (metabolism) Neoplasm Invasiveness Retinoid X Receptor gamma (metabolism) Tretinoin (administration & dosage, analogs & derivatives) Valproic Acid (administration & dosage) bcl-2-Associated X Protein (metabolism)

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