Review Article

Therapeutic Implications of PPAR in Human Osteosarcoma

Table 2

Potential effects of nuclear receptor ligands on osteosarcoma tumors.

LigandExperimental SetupEffectMechanismReference

PPARγTroglitazonein vitro proliferation and apoptosis assaysinhibited proliferationpromotion of apoptosis, induce differentiation (alkaline phosphatase)Haydon 2002, 2007 [9, 32]
Ciglitazonein vitro proliferation and apoptosis assaysminimal effectunknownHaydon2002 [32]
Troglitazonein vitro MTT proliferation and apoptosis assaysincreased proliferationinhibition of apoptosisLucarelli 2002 [170]
Pioglitazone and PG J(2)in vitro MTT and apoptosis assays of Chondrosarcoma Cellsinhibition of proliferationpromoted apoptosisNishida [171]

Retinoic Acid9-cis retinoic acidin vitro proliferation and apoptosis assaysinhibited proliferationpromotion of apoptosisHaydon 2002, 2007 [9, 32]

Estrogen17-beta estradiol, OspemifeneU2OS expressing ER, in vitro apoptosis assaysopposed Etoposide-induced cell deathoppose increases in IL-6 and decreases in OPG, preventing osteoclast activationKallio 2008 [172]
Tamoxifen, RaloxifeneU2OS expressing ER, in vitro apoptosis assaysno effect on Etoposide-induced cell deathunknownKallio 2008 [172]
17-beta estradiol, SERMS (genistein, daidzein)U2OS expressing ER, in vitro cell cycle, proliferation, apoptosis assaysinhibit proliferation, promote apoptosisdecrease EGFR, increased osteoblast maturation markersSalvatori 2009 [173]

Vitamin D1-alpha hydroxyvitamin D3oral administration in Dunn murine OS modelinhibits tumor growth and metastasisincreased necrosis, no cell cycle mitotic index effectsHara 2001 [174]
Prolactin + 1,25 (OH)2 Vitamin D3RT-PCR, western blotsPRL inhibits VDR expression in response to 1,25 (OH)2 Vitamin D3VDR expression is dependent on BRCA1 expressionDeng [175]
calcitriolOS cells with increased RXR degradation, treated with calcitriolincreased expression of RXR restores anti-proliferative effects of calcitriolcalcitriol induced degradation is dependent on RXR expressionPrufer 2002 [176]