PMID- 19288012
OWN - NLM
STAT- MEDLINE
DCOM- 20090618
LR  - 20190606
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 21
IP  - 4
DP  - 2009 Apr
TI  - Enhanced effects of PPARgamma ligands and RXR selective retinoids in combination 
      to inhibit migration and invasiveness in cancer cells.
PG  - 1083-9
AB  - Experimental data from in vitro and in vivo models indicate that peroxisome 
      proliferator-activated receptor (PPAR) ligand activation regulates 
      differentiation and induces cell growth arrest and apoptosis in a variety of 
      cancer types. Thiazolidinediones such as ciglitazone (CGZ) constitute the most 
      well-known synthetic ligands for PPARgamma. We previously reported a remarkable 
      antitumor effect of the retinoid 6-OH-11-O-hydroxyphenantrene (IIF), synthetic 
      retinoid X receptors (RXRs) agonist, on many cancer cell lines. Since PPARs bind 
      to DNA as heterodimers with RXRs, in this study we investigated if IIF 
      potentiates the antitumoral properties of the PPARgamma ligand CGZ in 
      glioblastoma U87MG and melanoma G361 cells. Our results show that either IIF or 
      CGZ inhibited cell growth and tissue invasion ability, but these properties were 
      enhanced by using IIF and CGZ in combined treatment. Since matrix 
      metalloproteinases (MMPs) play a major role in tumor cell invasion, we analyzed 
      the effect of IIF and CGZ on MMP2 and MMP9 activity and expression. The addition 
      of IIF to CGZ resulted in a decrease of MMP2 and MMP9 expression and activity, 
      higher than when each agent was used alone. Furthermore, treatment with IIF 
      and/or CGZ enhanced PPARgamma expression but both agents in combined treatment 
      caused the maximum efficiency. Finally, we demonstrated that IIF can potentiate 
      PPARgamma trascriptional activity induced by CGZ, by evaluation of peroxisome 
      proliferator-responsive element transactivation. In conclusion, these findings 
      suggest that the RXR selective retinoid IIF, in combination with the PPARgamma 
      ligand CGZ, may provide a therapeutic advantage in cancer treatment.
FAU - Papi, A
AU  - Papi A
AD  - Department of Experimental Evolutionary Biology, University of Bologna, 40126 
      Bologna, Italy.
FAU - Rocchi, P
AU  - Rocchi P
FAU - Ferreri, A M
AU  - Ferreri AM
FAU - Guerra, F
AU  - Guerra F
FAU - Orlandi, M
AU  - Orlandi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents)
RN  - 0 (IIF compound)
RN  - 0 (PPAR gamma)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Thiazolidinediones)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - U8QXS1WU8G (ciglitazone)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Drug Synergism
MH  - Humans
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasms/*drug therapy/pathology
MH  - PPAR gamma/*agonists/physiology
MH  - Retinoid X Receptors/*agonists/physiology
MH  - Thiazolidinediones/*administration & dosage
MH  - Tretinoin/administration & dosage/*analogs & derivatives
EDAT- 2009/03/17 09:00
MHDA- 2009/06/19 09:00
CRDT- 2009/03/17 09:00
PHST- 2009/03/17 09:00 [entrez]
PHST- 2009/03/17 09:00 [pubmed]
PHST- 2009/06/19 09:00 [medline]
AID - 10.3892/or_00000327 [doi]
PST - ppublish
SO  - Oncol Rep. 2009 Apr;21(4):1083-9. doi: 10.3892/or_00000327.