Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells

Kutbay, Nilüfer Özdemir; Avci, Çığır Biray; Yürekli, Banu Şarer; Kurt, Cansu Çalışkan; Shademan, Behrouz; Gündüz, Cumhur; Erdoğan, Mehmet

doi:10.1002/jbt.22547

Cited by 23 publications

(15 citation statements)

References 53 publications

(80 reference statements)

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“…CTC, isobologram, and isobolographic analyses are used in weeding (Gao et al, 2011; Zhao et al, 2018) and memory enhancement (Johnson et al, 2011; Ahmadi-Mahmoodabadi et al, 2016; Nasehi et al, 2017), as well as analgesic (An-Kuo et al, 2018; Basting et al, 2019; Chou et al, 2019; Eiselt et al, 2019; JI et al, 2017; Li et al, 2019), antioxidant (JI et al, 2017; Yao et al, 2017), anti-inflammation (Rakariyatham et al, 2018), anticancer property examination (Chao et al, 2019; Şiğva et al, 2019), cytotoxicity (Tatay et al, 2014; Sir et al, 2018; Hoover et al, 2019), and thyroid examination (Nilufer Ozdemir Kutbay et al, 2017). The analytical methods and other methods used to evaluate drug interactions are shown in Table 1 .…”

Section: Application Of Isobologram Analysis To Evaluate Drug Interacmentioning

confidence: 99%

Isobologram Analysis: A Comprehensive Review of Methodology and Current Research

et al. 2019

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Drug combination is a common method for clinical disease treatment. Whether the combination of drugs is reasonable often affects the result of the disease treatment. Many methods have been used to evaluate interaction between drugs to date. Isobologram analysis has been mathematically proven and widely used to evaluate drug interactions. In this paper, the principle of isobologram analysis and its application in drug interaction evaluation are summarized. The applications of the similar cotoxicity coefficient and fractional inhibitory concentration index in the evaluation of drug interaction are also reviewed. This work is expected to evaluate the effect of formulations scientifically and provide scientific judgment standards for the development of formulations and clinical drug compatibility.

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Section: Application Of Isobologram Analysis To Evaluate Drug Interacmentioning

confidence: 99%

Isobologram Analysis: A Comprehensive Review of Methodology and Current Research

et al. 2019

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“…Ozdemir et al. ( 34 ). find tumor suppressor genes, including DDIT4L , that are significantly elevated in the metformin and pioglitazone combination-treated anaplastic thyroid cancer cells.…”

Section: Discussionmentioning

confidence: 99%

A Novel Multi-Omics Analysis Model for Diagnosis and Survival Prediction of Lower-Grade Glioma Patients

Wang

Xiang

et al. 2022

Front. Oncol.

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BackgroundLower-grade gliomas (LGGs) are characterized by remarkable genetic heterogeneity and different clinical outcomes. Classification of LGGs is improved by the development of molecular stratification markers including IDH mutation and 1p/19q chromosomal integrity, which are used as a hallmark of survival and therapy sensitivity of LGG patients. However, the reproducibility and sensitivity of the current classification remain ambiguous. This study aimed to construct more accurate risk-stratification approaches.MethodsAccording to bioinformatics, the sequencing profiles of methylation and transcription and imaging data derived from LGG patients were analyzed and developed predictable risk score and radiomics score. Moreover, the performance of predictable models was further validated.ResultsIn this study, we determined a cluster of 6 genes that were correlated with IDH mutation/1p19q co-deletion status. Risk score model was calculated based on 6 genes and showed gratifying sensitivity and specificity for survival prediction and therapy response of LGG patients. Furthermore, a radiomics risk score model was established to noninvasively assist judgment of risk score in pre-surgery. Taken together, a predictable nomogram that combined transcriptional signatures and clinical characteristics was established and validated to be preferable to the histopathological classification. Our novel multi-omics nomograms showed a satisfying performance. To establish a user-friendly application, the nomogram was further developed into a web-based platform: https://drw576223193.shinyapps.io/Nomo/, which could be used as a supporting method in addition to the current histopathological-based classification of gliomas.ConclusionsOur novel multi-omics nomograms showed the satisfying performance of LGG patients and assisted clinicians to draw up individualized clinical management.

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“…Gemigliptin increased metformin-mediated inhibition of proliferation and migration through MMP9, VCAM-1 and p-ERK reduction and p53 and p21 increase [17]. In ATC cells, combination of metformin with pioglitazone decreased expression of AKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C and PRKCA and increased expression of some tumor suppressor genes (e.g., EIF4EBP1, EIF4EBP2, PTEN) [45]. Pioglitazone is an insulin sensitizer for type 2 diabetes with therapeutic effects in mouse models of thyroid cancer due to the fusion protein (PAX8-PPARg) present in 30% of thyroid cancer [46].…”

Section: Thyroid Cancermentioning

confidence: 97%

“…Metformin has a plethora of molecular actions in prostate cancer cell lines, as shown in Figure 1. The best described is induction of AMPKα phosphorylation (Thr172), regulating downstream targets, such as acetyl-CoA carboxylase (ACC), ACC2, S6, S6K1, mTORC1 and SREBP1c [40][41][42][43][44][45][46][47][48][49][50][51][52][53]. Metformin promotes glucose fermentation (glucose uptake, lactate formation and increased glycolysis rate) in prostate cancer cell lines, inhibiting mitochondrial complex I (component of the electron transport chain) and oxygen consumption [54][55][56].…”

Section: Prostate Cancermentioning

confidence: 99%

Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models

2022

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Metformin is the most used drug for type 2 diabetes (T2DM). Its antitumor activity has been described by clinical studies showing reduced risk of cancer development in T2DM patients, as well as management of T2DM compared with those receiving other glucose-lowering drugs. Metformin has a plethora of molecular actions in cancer cells. This review focused on in vitro data on the action mechanisms of metformin on thyroid, prostate and head and neck cancer. AMPK activation regulating specific downstream targets is a constant antineoplastic activity in different types of cancer; however, AMPK-independent mechanisms are also relevant. In vitro evidence makes it clear that depending on the type of tumor, metformin has different actions; its effects may be modulated by different cell conditions (for instance, presence of HPV infection), or it may regulate tissue-specific factors, such as the Na+/I− symporter (NIS) and androgen receptors. The hallmarks of cancer are a set of functional features acquired by the cell during malignant development. In vitro studies show that metformin regulates almost all the hallmarks of cancer. Interestingly, metformin is one of these therapeutic agents with the potential to synergize with other chemotherapeutic agents, with low cost, low side effects and high positive consequences. Some questions are still challenging: Are metformin in vitro data able to translate from bench to bedside? Does metformin affect drug resistance? Can metformin be used as a generic anticancer drug for all types of tumors? Which are the specific actions of metformin on the peculiarities of each type of cancer? Several clinical trials are in progress or have been concluded for repurposing metformin as an anticancer drug. The continuous efforts in the field and future in vitro studies will be essential to corroborate clinical trials results and to elucidate the raised questions.

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Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells

Cited by 23 publications

References 53 publications

Isobologram Analysis: A Comprehensive Review of Methodology and Current Research

Isobologram Analysis: A Comprehensive Review of Methodology and Current Research

A Novel Multi-Omics Analysis Model for Diagnosis and Survival Prediction of Lower-Grade Glioma Patients

Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models

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