The PPARγ ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines

Morosetti, Roberta; Servidei, Tiziana; Mirabella, Massimiliano; Rutella, Sergio; Mangiola, Annunziato; Maira, Giulio; Mastrangelo, Renato; Koeffler, H. Phillip

doi:10.3892/ijo.25.2.493

Cited by 39 publications

(42 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is thought that PGD 2 and its other metabolites like 15-deoxy-D 12,14 -prostaglandin J 2 exert their cell death effect through the peroxisome proliferator-activated receptor g (30). Previous studies have documented high expression levels of peroxisome proliferator-activated receptor g in high-grade brain tumors (31) as well as in the A172 cell line that we used for our in vitro studies (32). Interestingly, when PGD 2 was added to A172 cells, the observed cell death was not mediated through the apoptotic pathway.…”

Section: Discussionmentioning

confidence: 93%

Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma

Payne

Maleki

Messina

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D 2 (PGD 2 ) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD 2 , to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD 2 substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas. [Mol Cancer Ther 2008;7(10):3420 -8]

show abstract

Section: Discussionmentioning

confidence: 93%

Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma

Payne

Maleki

Messina

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Rosiglitazone has been shown to inhibit the growth of several human cancer cells through PPARg-dependent signals (26,35,36). Ferruzzi et al (26) found that rosiglitazone inhibited the growth and invasiveness of human adrenocortical cancer cells through activation of PPARg.…”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone suppresses human lung carcinoma cell growth through PPARγ-dependent and PPARγ-independent signal pathways

Han

Roman

2006

Molecular Cancer Therapeutics

153

131

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors ; (PPAR;) exert diverse effects on cancer cells. Recent studies showed that rosiglitazone, a synthetic ligand for PPAR;, inhibits cell growth. However, the exact mechanisms underlying this effect are still being explored, and the relevance of these findings to lung cancer remains unclear. Here, we report that rosiglitazone reduced the phosphorylation of Akt and increased phosphatase and tensin homologue (PTEN) protein expression in nonsmall cell lung carcinoma (NSCLC) cells (H1792 and H1838), and this was associated with inhibition of NSCLC cell proliferation. These effects were blocked or diminished by GW9662, a specific PPAR; antagonist. However, transfection with a CMX-PPAR;2 overexpression vector restored the effects of rosiglitazone on Akt, PTEN, and cell growth in the presence of GW9662. In addition, rosiglitazone increased the phosphorylation of AMP-activated protein kinase A (AMPKA), a downstream kinase target for LKB1, whereas it decreased phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream target of mammalian target of rapamycin (mTOR). Of note, GW9662 did not affect the phosphorylation of AMPKA and p70S6K protein. The inhibitory effect of rosiglitazone on NSCLC cell growth was enhanced by the mTOR inhibitor rapamycin; however, it was blocked, in part, by the AMPKA small interfering RNA. Taken together, these findings show that rosiglitazone, via up-regulation of the PTEN/AMPK and down-regulation of the Akt/mTOR/p70S6K signal cascades, inhibits NSCLC cell proliferation through PPAR;-dependent and PPAR;-independent signals. [Mol Cancer Ther 2006;5(2):430 -7]

show abstract

“…This also prevents the downregulation of COX-2, which when elevated can have a pronounced effect on microvessel density and angiogenesis in prostatic tumors (Kirschenbaum et al 2001. PGD 2 -induced cell proliferation and PGJ 2 -induced differentiation and programmed cell death have been identified in variety of cell types including prostate cancer cells (Butler et al 2000, Desmond et al 2003, Yee et al 2003, Morosetti et al 2004, Zang et al 2004. Furthermore, the activation of PPARg by a synthetic ligand, troglitazone, suppressed AR trans-activation activity in prostate cancer cells and serum prostate-specific antigen levels in a patient with CaP (Hisatake et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of type 2 3α-hydroxysteroid dehydrogenase/type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma

Fung¹,

Samara²,

Wong³

et al. 2006

Endocr Relat Cancer

114

View full text Add to dashboard Cite

Type 2 3a-hydroxysteroid dehydrogenase (3a-HSD) is a multi-functional enzyme that possesses 3a-, 17b-and 20a-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3a-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of D 4 -androstene-3,17-dione to testosterone, 5a-dihydrotestosterone to 5a-androstane-3a,17b-diol (3a-diol), and 3a-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence transactivation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.

show abstract

The PPARγ ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines

Cited by 39 publications

References 0 publications

Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma

Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma

Rosiglitazone suppresses human lung carcinoma cell growth through PPARγ-dependent and PPARγ-independent signal pathways

Increased expression of type 2 3α-hydroxysteroid dehydrogenase/type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma

Contact Info

Product

Resources

About