Table 2.

PPAR-independent effects on tumor-related genes.

PPARs ligand	PPAR-independent effect	Experimental strategies	Ref.
PPARγ ligands
Troglitazone in LNCaP prostate cancer cells	Androgen receptor (AR) suppression by facilitating the ubiquitin-dependent proteasomal degradation of the transcriptional factor Sp-1	STG28, a PPARγ-inactive analogue of troglitazone.	[143]
Troglitazone in mice	Rapidly AMP-activated protein kinase (AMPK) activation through a yet undefined PPAR-γ-independent mechanism, leading to the suppression of insulin-like growth factor-I tumor-promoting activity (IGF-1)	Expression of a dominant-negative AMPK	[144]
Troglitazone and ciglitazone in MCF-7 breast cancer	Repression of cyclin D1 expression, though a post transcriptional mechanism, via proteasome-facilitated proteolysis	Proteasome inhibitors	[145]
Ciglitazone in HT1080 human fibrosarcoma	Increase of MMP-2 expression through ROS production and ERK activation	PPARγ antagonist GW9662	[146]
Troglitazone and 15-deoxy-prostaglandin J2 (15dPGJ2) in prostate and bladder cancer cells	Troglitazone induces G0/G1 growth arrest and PGJ2 induces apoptosis	PPARγ antagonist GW9662	[147]
Troglitazone in B cell acute lymphoblastic leukemia cell lines	Apoptosis and cell growth inhibition associated with G1 cell cycle arrest	PPAR antagonists	[148]
Thiazolidinediones (TZD) in human breast cancer	Inhibition of Cyclin D3 expression by decreasing cyclin mRNA levels and by inducing its proteasomal degradation	A dominant negative mutant of PPARγ	[149]
Troglitazone in mouse skin keratinocytes	Inhibition of cyclin D1 expression	PPARγ antagonist GW9662 and dominant Dominant negative PPARγ.	[150]
Thiazolidinediones (TGZ) in human colon cancer cells HTC-116	Egr-1 promoter activity increase	Different PPARγ ligands	[140]
15-deoxy-prostaglandin J2 (15dPGJ2) in colon carcinoma cells	COX2 and VEGF inhibition via AP-1 activity repression	Dominant negative form of PPARγ and a PPARγ antagonist	[151]
15-deoxy-prostaglandin J2 (15dPGJ2) induces apoptosis in human B lymphocytes	Apoptosis through the induction of ROS and depletion of glutathione	Dominant negative form of PPARγ and a PPARγ antagonist	[152]
15-deoxy-prostaglandin J2 (15dPGJ2) in Jurkat human leukemic cells and PC3 human prostate cancer cells	Apoptosis by increasing the mRNA stability of death Receptor 5 (DR5), a specific receptor for tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL)	PPARγ antagonist GW9662	[153]
PPARα ligands
DEHP in mice	Induction of hepatic tumorigenesis	Wild-type and PPARα-null mice in comparison	[154]
WY14,643 in activated splenocytes isolated from C57BL/6 mice	Apoptosis	Wild-type and PPARα-null mice in comparison	[155]
PPARβ/δ ligands
GW0742 in PPARβ-null mouse model	Induction of keratinocyte terminal differentiation and inhibition of keratinocyte proliferation	PPARδ-null mice	[86]