Ceramide induces apoptosis via a peroxisome proliferator-activated receptor γ-dependent pathway

Wang, Jing; Lv, Xin; Shi, Jieping; Hu, Xiaosong

doi:10.1007/s10495-006-0191-9

Cited by 16 publications

(10 citation statements)

References 41 publications

(38 reference statements)

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“…Activation of PPARγ by its ligands can induce growth inhibition and cytotoxicity in human prostate cancer cells, colon cancer cells and liposarcoma cells, and their biological activities are attributed to inhibition of proliferation and induction of apoptosis by PPARγ [21,22] . We have previously shown C2-ceramide could induce apoptosis via a PPARγ dependent pathway in human colon cancer HT29 cells [14] . To examine whether the PPARγ pathway was involved in the modulation of cell cycle arrest induced by ceramide in human hepatocarcinoma Bel7402 cells, the luciferase reporter of PPRE3x-tk-luc was transfected and luciferase activity was assayed.…”

Section: Discussionmentioning

confidence: 97%

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Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

Wang

Lv²,

Shi³

et al. 2007

WJG

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AIM:To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS:[ 3 -( 4 , 5 ) -d i m e t h y l t h i a z o l -2 -y l ] -2 , 5-diphenyltetrazolium bromide (MTT) assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.RESULTS: C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERK1/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, w h i l e t h e t ra n s c r i p t i o n a l a c t i v i ty o f P PA R γ w a s upregulated. Addition of GW9662, which is a PPARγ specific antagonist, could reserve the modulation action on CDK7. CONCLUSION:Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARγ activation. The ERK signaling pathway was involved in this process.

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Section: Discussionmentioning

confidence: 97%

“…In our previous study, we reported that C2-ceramide could activate PPARγ transcription activity in human colon cancer HT29 cells [14] . In this study, as shown in Figure 3A, C2-ceramide could also markedly activate the transcriptional activity of PPARγ in hepatocarcinoma Bel7402 cells.…”

Section: Cdk7 and Pparγ Pathways Involved In Cell Cycle Arrest Inducementioning

confidence: 94%

Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

Wang

Lv²,

Shi³

et al. 2007

WJG

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“…A well establish pharmacological effect of NSAIDs is inhibition of prostaglandin synthesis by inhibiting cyclooxygenase (COX) activity [12]. NSAIDs induce COX-2-dependent apoptosis by activating PPARs (peroxisome proliferator activated receptors), intracellular receptors that modulate apoptosis in a variety of cell types [13], increasing cellular concentrations of arachidonic acids, a substrate of COX-2, leading to conversion of sphingomyelin to ceramide, a potent apoptosis inducer [14,15], or altering mitochondrial permeability and cytochrome c release [16]. NSAIDs also induce apoptosis via COXindependent pathways.…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of GADD45α expression by NSAIDs leads to apoptotic and necrotic colon cancer cell deaths

Chiou

Hoa

2009

Apoptosis

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Growth arrest and DNA damage inducible 45 alpha (GADD45alpha) is a central player in mediating apoptosis induced by a variety of stress stimuli and genotoxic agents. Regular usage of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and sulindac is associated with reduced risk for various cancers, including colon cancer. The role of GADD45alpha in NSAID-induced colon cancer cell cytotoxicity is unknown. In this study, we report that indomethacin and sulindac sulfide treatments up-regulate GADD45alpha mRNA expression and protein levels in colon cancer HT-29, RKO and Caco-2 cells. This up-regulation of GADD45alpha is accompanied by necrotic cell death and apoptosis. Anti-sense suppression of GADD45alpha expression inhibited indomethacin and sulindac sulfide-induced necrotic cell death and apoptosis. These findings confirm a role for GADD45alpha in NSAID-induced cytotoxicity, a mechanism for the anti-neoplastic effect of NSAIDs in colon tumorigenesis and cancer growth.

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“…Endocrine organs targeted by EDCs include the reproductive organs, heart, pancreas, thyroid, parathyroid, adrenal glands, hormone dependent metabolic system (pancreas and liver) and effects on brain function. Particular interest in EDCs such as phthalates in the regulation of the PPAR gamma (nuclear receptors) in adipose tissue indicates that they play an important role in the induction of obesity [114]- [119] similar to ceramide-PPAR interactions in cellular apoptosis and insulin resistance [10] [120]. The effects of EDCs on Sirt1-PPAR (alpha or gamma) interactions and their effects on the endocrine system have been reported with endocrine disorders linked to chronic diseases connected to appetite dysregulation and behavioural disorders.…”

Section: Endocrine Disruptors As Risk Factors For Obesity and Chronicmentioning

confidence: 99%

Induction of NAFLD with Increased Risk of Obesity and Chronic Diseases in Developed Countries

Martins¹

2014

OJEMD

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The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be involved in cell suicide in various organ diseases with the importance of accelerated aging that requires early intervention with drug therapy to prevent diseases such as non alcoholic fatty liver disease (NAFLD) that has increased in children and reached to approx. 40% of the global population. Obesity is induced by various diets and lifestyle factors such as stress, anxiety and depression which are important to consider with the global increase in obesity and are possibly linked to the rise in individuals with brain disorders that involve neurodegeneration. Xenobiotics such as the endocrine disruptor chemicals that have increased in the environment in various developed countries lead to various chronic endocrine diseases as populations divert towards unhealthy diets and lifestyles with induction of NAFLD and obesity. The amount and nature of food intake that improves and increases liver lipid and xenobiotic metabolism in obese individuals have become important to decrease the risk for increased adiposity in man. High fibre or protein diets that contain leucine may improve liver glucose, lipid and xenobiotic metabolism and require further investigation with xenobiotics such as endocrine disruptors involved in appetite dysregulation and metabolic disorders in developed countries. The use of anti-obese drugs that reduce food intake and improve hypercholesterolemia and cardiovascular disease has been assessed in obesity with drug therapy closely involved either in the prevention or induction of NAFLD and obesity in man.

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Ceramide induces apoptosis via a peroxisome proliferator-activated receptor γ-dependent pathway

Cited by 16 publications

References 41 publications

Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

Up-regulation of GADD45α expression by NSAIDs leads to apoptotic and necrotic colon cancer cell deaths

Induction of NAFLD with Increased Risk of Obesity and Chronic Diseases in Developed Countries

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