Thiazolidenediones induce tumour-cell apoptosis through the Akt-GSK3β pathway

Zhu, Hong; Han, Bing; Pan, Xian-Zhen; Qi, Hui; Luo, Xu

doi:10.1111/j.1365-2710.2011.01251.x

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Furthermore, glitazones inactivated GSK-3b, which exerts essential roles in prostate cancer growth and in androgen-independent phenotype (Zhu et al 2012). Very noteworthy, the GSK-3b inhibitor lithium sensitized prostate cancer cells to glitazone cytotoxicity (Zhu et al 2012). Antioxidant edible anthocyanins reduce obesity and the severity of the metabolic syndrome (Qin and Anderson 2012).…”

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

confidence: 98%

“…The apoptosis-triggering efficacy of glitazones on prostate cancer cells involved the inhibition of Akt phosphorylation. Furthermore, glitazones inactivated GSK-3b, which exerts essential roles in prostate cancer growth and in androgen-independent phenotype (Zhu et al 2012). Very noteworthy, the GSK-3b inhibitor lithium sensitized prostate cancer cells to glitazone cytotoxicity (Zhu et al 2012).…”

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: 98%

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

confidence: 99%

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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“…Previous studies showed that LiCl also possess antineoplastic effects in a variety of cancers including colorectal cancer [ 10 ], gastric cancer [ 11 ], and neuroblastoma [ 12 ]. It was shown that anti-neoplastic action of LiCl primarily depends on the inhibition of glycogen synthase kinase 3-beta [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinomain vitro

et al. 2011

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ObjectiveThe aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies.MethodsImatinib mesylate (50 µM), lithium chloride (100 µM), medroxyprogesterone acetate (200 µM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student's t-test.ResultsAll drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05).ConclusionThe present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense.

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The impact of thiazolidinediones on the risk for prostate cancer in patients with type 2 diabetes mellitus: A review and meta-analysis

Nath

Choudhury

2021

Meta Gene

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Thiazolidenediones induce tumour-cell apoptosis through the Akt-GSK3β pathway

Cited by 4 publications

References 26 publications

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

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

Combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinomain vitro

The impact of thiazolidinediones on the risk for prostate cancer in patients with type 2 diabetes mellitus: A review and meta-analysis

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