Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells

Yin, Fen; Bruemmer, Dennis; Blaschke, Florian; Hsueh, Willa A.; Law, Ronald E.; Herle, André J. Van

doi:10.1038/sj.onc.1207598

Cited by 79 publications

(76 citation statements)

References 40 publications

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“…[21][22][23] Among them, the GADD 45 family of genes, which is involved in the regulation of growth, DNA repair, and induction of apoptosis, 24 was upregulated in response to PL treatment. PL also modulated the expression of many cell signaling molecules, such as mitogenactivated protein kinases in the pancreatic cancer cells, which is in support of previous studies showing that PL modulates cell signaling pathways to lead to enhanced cancer cell death.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways

Dhillon

Mamidi

McClean

et al. 2016

Journal of Medicinal Food

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Piperlongumine (PL), an alkaloid obtained from long peppers, displays antitumorigenic properties for a variety of human cell-and animal-based models. The aim of this study was to identify the underlying molecular mechanisms for PL anticancer effects on human pancreatic cancer cells. RNA sequencing (RNA-seq) was used to identify the effects of PL on the transcriptome of MIA PaCa-2 human pancreatic cancer cells. PL treatment of pancreatic cancer cells resulted in differential expression of 683 mRNA transcripts with known protein functions, 351 of which were upregulated and 332 of which were downregulated compared to control-treated cells. Transcripts associated with oxidative stress, endoplasmic reticulum (ER) stress, and unfolded protein response pathways were significantly overexpressed with PL treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to validate the RNA-seq results, which included upregulation of HO-1, IRE1a, cytochrome c, and ASNS. The results provide key insight into the mechanisms by which PL alters cancer cell physiology and identify that activation of oxidative stress and ER stress pathways is a critical avenue for PL anticancer effects.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways

Dhillon

Mamidi

McClean

et al. 2016

Journal of Medicinal Food

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“…Indeed, PPARg independent inhibition of cell proliferation and induction of apoptosis have been attributed to Tzds such as troglitazone, rosiglitazone, and ciglitazone. Such mechanisms include inhibition of cyclin D3 and survivin in breast cancer (Lu et al, 2005) upregulation of GADD45 in breast cancer (Yin et al, 2004), enhanced reactive oxygen species in gliomas (Perez-Ortiz et al, 2004) and ablation of cyclin D1 in breast cancer . In fact, the first generation Tzd, troglitazone, is also a vitamin E (atocopherol) analog and was originally synthesized in efforts to identify novel antioxidants (Fujiwara et al, 1998;Davies et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Novel high-affinity PPARγ agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1

et al. 2005

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Peroxisomeproliferator-activated receptor gamma (PPARc) agonists demonstrate antitumor activity likely through transactivating genes that regulate cell proliferation, apoptosis, and differentiation. The PAX8/PPARc fusion oncogene, which is common in human follicular thyroid carcinomas appears to act via dominant negative suppression of wild-type PPARc, suggesting that it may be a tumor suppressor gene in thyroid cells. We have identified a novel high-affinity PPARc agonist (RS5444) that is dependent upon PPARc for its biological activity. This is the first report of this molecule and its antitumor activity. In vitro, the IC 50 for growth inhibition is B0.8 nM while anaplastic thyroid carcinoma (ATC) tumor growth was inhibited threeto fourfold in nude mice. siRNA against PPARc and a pharmacological antagonist demonstrated that functional PPARc was required for growth inhibitory activity of RS5444. RS5444 upregulated the cell cycle kinase inhibitor, p21 WAF1/CIP1 . Silencing p21 WAF1/CIP1 rendered cells insensitive to RS5444. RS5444 plus paclitaxel demonstrated additive antiproliferative activity in cell culture and minimal ATC tumor growth in vivo. RS5444 did not induce apoptosis but combined with paclitaxel, doubled the apoptotic index compared to that of paclitaxel. Our data indicate that functional PPARc is a molecular target for therapy in ATC. We demonstrated that RS5444, a thiazolidinedione (Tzd) derivative, alone or in combination with paclitaxel, may provide therapeutic benefit to patients diagnosed with ATC.

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“…Thus, cotreatment with EGCG plus celecoxib induced high upregulation of only GADD153 gene expression, although p21 WAF1 and GADD45 genes are also apoptosis related genes in PC-9 cells. 21,22 Thus, GADD153 is a unique biomarker, induced by EGCG and celecoxib cooperatively.…”

Section: Upregulation Of Gadd153 Expression By Cotreatment With Egcg mentioning

confidence: 99%

Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation of GADD153 gene

Suganuma

Kurusu

Suzuki

et al. 2006

Intl Journal of Cancer

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To more clearly understand the molecular mechanisms involved in synergistic enhancement of cancer preventive activity with the green tea polyphenol (2)-epigallocatechin gallate (EGCG), we examined the effects of cotreatment with EGCG plus celecoxib, a cyclooxygenase-2 selective inhibitor. We specifically looked for induction of apoptosis and expression of apoptosis related genes, with emphasis on growth arrest and DNA damage-inducible 153 (GADD153) gene, in human lung cancer cell line PC-9: Cotreatment with EGCG plus celecoxib strongly induced the expression of both GADD153 mRNA level and protein in PC-9 cells, while neither EGCG nor celecoxib alone did. However, cotreatment did not induce expression of other apoptosis related genes, p21 WAF1 and GADD45. Judging by upregulation of GADD153, only cotreatment with EGCG plus celecoxib synergistically induced apoptosis of PC-9 cells. Synergistic effects with the combination were also observed in 2 other lung cancer cell lines, A549 and ChaGo K-1. Furthermore, EGCG did not enhance GADD153 gene expression or apoptosis induction in PC-9 cells in combination with N-(4-hydroxyphenyl)retinamide or with aspirin. Thus, upregulation of GADD153 is closely correlated with synergistic enhancement of apoptosis with EGCG. Cotreatment also activated the mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38 MAPK: Preteatment with PD98059 (ERK1/2 inhibitor) and UO126 (selective MEK inhibitor) abrogated both upregulation of GADD153 and synergistic induction of apoptosis of PC-9 cells, while SB203580 (p38 MAPK inhibitor) did not do so, indicating that GADD153 expression was mediated through the ERK signaling pathway. These findings indicate that high upregulation of GADD153 is a key requirement for cancer prevention in combination with EGCG. ' 2006 Wiley-Liss, Inc.Key words: EGCG; apoptosis; ERK1/2; prevention (2)-Epigallocatechin gallate (EGCG), a main constituent of green tea polyphenol, can act synergistically with cancer preventive agents (such as sulindac and tamoxifen) in inducing apoptosis of lung, colon and breast cancer cells. 1-3 Since EGCG and green tea have a wide range of target organs and are nontoxic for animals and humans, there is growing interest in increasing the antitumor activity of cancer preventive agents in combination with EGCG or green tea. [4][5][6] However, the molecular mechanisms responsible for the synergistic effects of cotreatment with EGCG plus cancer preventive agents are not known. Using human cDNA cancer expression array, we have found upregulated expressions of 2 genes, growth arrest and DNA damage-inducible gene 153 (GADD153) and p21 WAF1 , and downregulated expressions of 4 genes, T-plasminogen activator, TIMP3, IL-1b and integrin b4: All of these genes are associated with synergistic induction of apoptosis of human non-small-cell lung carcinoma (NSCLC) cell line PC-9 by cotreatment with EGCG plus sulindac. 7 Treatment with either EGCG or sulindac alone did not affect these gene expressions. Since upregulation of GADD153 gene expressi...

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Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells

Cited by 79 publications

References 40 publications

Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways

Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways

Novel high-affinity PPARγ agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1

Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation of GADD153 gene

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