Troglitazone, a PPAR agonist, inhibits human prostate cancer cell growth through inactivation of NFκB via suppression of GSK-3β expression

Ban, Jung Ok; Oh, Jiyoung; Son, Seung Mo; Won, Dohee; Song, Ho Seub; Han, Sang Bae; Moon, Dong Cheul; Kang, Keon Wook; Song, Min Jong; Hong, Jin Tae

doi:10.4161/cbt.12.4.15961

Cited by 35 publications

(25 citation statements)

References 35 publications

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“…The actions of troglitazone on the expression of PPAR-c, GSK-3b and NF-jB activity and prostate cancer cell proliferation were determined. Troglitazone induced the expression of PPAR-c in the nuclei of PC-3 cells, but not in LNCaP cells (Ban et al 2011). Troglitazone (0-16 lM) decreased cancer cell proliferation at similar rates in both cells via cell cycle arrest in G0/G1 phase and induced apoptosis in a concentration-dependent manner.…”

Section: Mutual Interactions Between Gsk-3b and Ppar-c Pathways And Rmentioning

confidence: 96%

“…Troglitazone inhibited the constitutive expression of GSK-3b and activation of NF-jB. Simultaneous treatment with troglitazone and a GSK-3b inhibitor or GSK-3b siRNA significantly increased troglitazone inhibition of the NF-jB activity, the reduction of prostate cancer cell proliferation and induction of apoptosis (Ban et al 2011). The effects of glitazones on apoptosis and on the serine/ threonine kinase pathway, Akt, and GSK-3b were examined in LNCaP cells.…”

Section: Mutual Interactions Between Gsk-3b and Ppar-c Pathways And Rmentioning

confidence: 99%

“…Molecular mechanisms of PPAR-c agonist-mediated anti-proliferative effects on prostate cancer cells were analyzed (Ban et al 2011). The actions of troglitazone on the expression of PPAR-c, GSK-3b and NF-jB activity and prostate cancer cell proliferation were determined.…”

Section: Mutual Interactions Between Gsk-3b and Ppar-c Pathways And Rmentioning

confidence: 99%

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A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

Elmacı

Altinöz²

2016

Biochem Genet

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Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L). L is used in psychiatric practice, yet also bears anti-diabetic potential and selectively inhibits glycogen synthase kinase-3 beta (GSK-3β). M, a biguanide class anti-diabetic agent shows anticancer activity via activating AMP-activated protein kinase (AMPK). Glitazones bind to PPAR-γ and inhibit NF-κB, triggering cell proliferation, apoptosis resistance and synthesis of inflammatory cytokines in cancer cells. Inhibition of inflammatory cytokines could simultaneously decrease tumor growth and alleviate cancer cachexia, having a major role in PC mortality. Furthermore, mutual synergistic interactions exist between PPAR-γ and GSK-3β, between AMPK and GSK-3β and between AMPK and PPAR-γ. In GBM, M blocks angiogenesis and migration in experimental models. Very noteworthy, among GBM patients with type 2 diabetes, usage of M significantly correlates with better survival while reverse is true for sulfonylureas. In experimental models, P synergies with ligands of RAR, RXR and statins in reducing growth of GBM. Further, usage of P was found to be lesser in anaplastic astrocytoma and GBM patients, indicating a protective effect of P against high-grade gliomas. L is accumulated in GBM cells faster and higher than in neuroblastoma cells, and its levels further increase with chronic exposure. Recent studies revealed anti-invasive potential of L in GBM cell lines. Here, we propose that a triple-agent regime including drugs already in clinical usage may provide a metabolic adjuvant therapy for PC and GBM.

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Section: Mutual Interactions Between Gsk-3b and Ppar-c Pathways And Rmentioning

confidence: 96%

Section: Mutual Interactions Between Gsk-3b and Ppar-c Pathways And Rmentioning

confidence: 99%

See 1 more Smart Citation

A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

Elmacı

Altinöz²

2016

Biochem Genet

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“…Although studies in colorectal and breast cancers have been disappointing, 101 troglitazone has shown its ability to inhibit human prostate cancer cell growth through inactivation of NF-κB via suppression of GSK-3β expression. 102 PPARγ is also involved in some thyroid cancers. A fusion protein of PPARγ1 and the thyroid transcription factor PAX8 is present in approximately one-third of follicular thyroid carcinomas, 103 and PPARγ activation by the agonist efatutazone (RS5444) inhibits anaplastic thyroid cancer (ATC) growth.…”

Section: Ppar Ligands As Antitumor Agentsmentioning

confidence: 99%

Anticancer Drugs That Modulate Hormone Action

Avendaño¹,

Menéndez²

2015

Medicinal Chemistry of Anticancer Drugs

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“…Other studies have also demonstrated that PPARγ agonists induce growtharrest by modulating the expression and activation of PPARγ in prostate cancer [30,31]. Troglitazone induces G0/G1 cell cycle arrest and apoptosis by blocking GSK3/nuclear factor κB pathways in prostate cancer [32]. Another study showed that lycopene up-regulates PPARγ-LXRα-ABCA1 pathway, suggesting its significance in the treatment of prostate cancer [33].…”

mentioning

confidence: 94%