PPARγ Activation by Troglitazone Enhances Human Lung Cancer Cells to TRAIL-induced Apoptosis Via Autophagy Flux

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 May 3

PMID 28460464

Citations 12

Authors

Uddin Md Nazim

Ji-Hong Moon

You-Jin Lee

Jae-Won Seol

Sang-Youel Park

Affiliations

Soon will be listed here.

Abstract

Members of the tumor necrosis factor (TNF) transmembrane cytokine superfamily, such as TNFα and Fas ligand (FasL), play crucial roles in inflammation and immunity. TRAIL is a member of this superfamily with the ability to selectively trigger cancer cell death but does not motive cytotoxicity to most normal cells. Troglitazone are used in the cure of type II diabetes to reduce blood glucose levels and improve the sensitivity of an amount of tissues to insulin. In this study, we revealed that troglitazone could trigger TRAIL-mediated apoptotic cell death in human lung adenocarcinoma cells. Pretreatment of troglitazone induced activation of PPARγ in a dose-dependent manner. In addition conversion of LC3-I to LC3-II and PPARγ was suppressed in the presence of GW9662, a well-characterized PPARγ antagonist. Treatment with troglitazone resulted in a slight increase in conversion rate of LC3-I to LC3-II and significantly decreased p62 expression levels in a dose-dependent manner. This indicates that troglitazone induced autophagy flux activation in human lung cancer cells. Inhibition of autophagy flux applying a specific inhibitor and genetically modified ATG5 siRNA enclosed troglitazone-mediated enhancing effect of TRAIL. These data demonstrated that activation of PPARγ mediated by troglitazone enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux and also suggest that troglitazone may be a combination therapeutic target with TRAIL protein in TRAIL-resistant cancer cells.

Citing Articles

PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges.

Zhang J, Tang M, Shang J Biomolecules. 2024; 14(2).

PMID: 38397426 PMC: 10886696. DOI: 10.3390/biom14020190.

An Antidepressant Drug Increased TRAIL Receptor-2 Expression and Sensitized Lung Cancer Cells to TRAIL-induced Apoptosis.

Zinnah K, Munna A, Seol J, Park B, Park S Anticancer Agents Med Chem. 2023; 23(20):2225-2236.

PMID: 37859313 PMC: 10788920. DOI: 10.2174/0118715206262252231004110310.

Regulation of Autophagy via Carbohydrate and Lipid Metabolism in Cancer.

Alizadeh J, Kavoosi M, Singh N, Lorzadeh S, Ravandi A, Kidane B Cancers (Basel). 2023; 15(8).

PMID: 37190124 PMC: 10136996. DOI: 10.3390/cancers15082195.

NSAIDs Induce Proline Dehydrogenase/Proline Oxidase-Dependent and Independent Apoptosis in MCF7 Breast Cancer Cells.

Kazberuk A, Chalecka M, Palka J, Bielawska K, Surazynski A Int J Mol Sci. 2022; 23(7).

PMID: 35409177 PMC: 8998922. DOI: 10.3390/ijms23073813.

Nonsteroidal Anti-Inflammatory Drugs as PPARγ Agonists Can Induce PRODH/POX-Dependent Apoptosis in Breast Cancer Cells: New Alternative Pathway in NSAID-Induced Apoptosis.

Kazberuk A, Chalecka M, Palka J, Surazynski A Int J Mol Sci. 2022; 23(3).

PMID: 35163433 PMC: 8835909. DOI: 10.3390/ijms23031510.

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