RT Journal Article
SR Electronic
T1 Anti-invasive Effects and Proapoptotic Activity Induction by the Rexinoid IIF and Valproic Acid in Combination on Colon Cancer Cell Lines
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2855
OP 2862
VO 32
IS 7
A1 A. PAPI
A1 A.M. FERRERI
A1 F. GUERRA
A1 M. ORLANDI
YR 2012
UL http://ar.iiarjournals.org/content/32/7/2855.abstract
AB 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.