NDLI: Apoptotic effect of the selective PPARβ/δ agonist GW501516 in invasive bladder cancer cells

Content Provider	Springer Nature Link
Author	Péchery, Adeline Fauconnet, Sylvie Bittard, Hugues Lascombe, Isabelle
Copyright Year	2016
Abstract	GW501516 is a selective and high-affinity synthetic agonist of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). This molecule promoted the inhibition of proliferation and apoptosis in few cancer cell lines, but its anticancer action has never been investigated in bladder tumor cells. Thus, this study was undertaken to determine whether GW501516 had antiproliferative and/or apoptotic effects on RT4 and T24 urothelial cancer cells and to explore the molecular mechanisms involved. Our results indicated that, in RT4 cells (derived from a low-grade papillary tumor), GW501516 did not induce cell death. On the other hand, in T24 cells (derived from an undifferentiated high-grade carcinoma), this PPARβ/δ agonist induced cytotoxic effects including cell morphological changes, a decrease of cell viability, a G2/M cell cycle arrest, and the cell death as evidenced by the increase of the sub-G1 cell population. Furthermore, GW501516 triggered T24 cell apoptosis in a caspase-dependent manner including both extrinsic and intrinsic apoptotic pathways through Bid cleavage. In addition, the drug led to an increase of the Bax/Bcl-2 ratio, a mitochondrial dysfunction associated with the dissipation of ΔΨm, and the release of cytochrome c from the mitochondria to the cytosol. GW501516 induced also ROS generation which was not responsible for T24 cell death since NAC did not rescue cells upon PPARβ/δ agonist exposure. For the first time, our data highlight the capacity of GW501516 to induce apoptosis in invasive bladder cancer cells. This molecule could be relevant as a therapeutic drug for high-grade urothelial cancers.
Starting Page	14789
Ending Page	14802
Page Count	14
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	11
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-09-16
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Bladder cancer Apoptosis PPARβ/δ GW501516 Reactive oxygen species Akt Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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