Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC δ-independent mechanism

Lim, Jun Hee; Woo, Seon Min; Min, Kyoung‐jin; Park, Eun Jung; Jang, Ji Hoon; Seo, Bo Ram; Iqbal, Taha; Lee, Tae-Jin; Kim, Sang Hyun; Choi, Yung Hyun; Kwon, Taeg Kyu

doi:10.1016/j.cbi.2012.02.003

Cited by 23 publications

(11 citation statements)

References 26 publications

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“…64,65,68,69 To ask whether it also played a role in the enhancement of the biological effects of ATRA by EVI1, U937_EVI1 and U937_vec cells were infected with retroviral vectors containing shRNAs against GDF15 (shGDF15-1, shGDF15-2) or against renilla luciferase as a control (shRen), and sorted for positivity for the vector encoded marker protein mCherry. qRT-PCR, immunoblot analysis, and ELISA confirmed a strong reduction of GDF15 mRNA and protein levels in ATRA treated U937_EVI1_shGDF15-1 and U937_EVI1_shGDF15-2 cells compared to U937_EVI1_ shRen cells (Fig.…”

Section: Evi1 Enhances Atra Induced Cell Cycle Arrest Differentiatiomentioning

confidence: 99%

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

Steinmetz¹,

Hackl²,

Slabáková³

et al. 2014

Cell Cycle

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The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-b superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects. The potential clinical implications of these findings are discussed.

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Section: Evi1 Enhances Atra Induced Cell Cycle Arrest Differentiatiomentioning

confidence: 99%

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

Steinmetz¹,

Hackl²,

Slabáková³

et al. 2014

Cell Cycle

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“…Kumar et al (21) reported that rottlerin induced autophagy and apoptosis via regulation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway in prostate and pancreatic cancer stem cells (22). Lim et al (23) found that rottlerin induced apoptosis via regulating extracellular signal regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in colon carcinoma cells. Another study showed that rottlerin inhibited cell growth and invasion through the downregulation of Cdc20 in glioma cells (24).…”

Section: Discussionmentioning

confidence: 99%

Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma

Shi

Ning

et al. 2017

Mol Med Report

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Rottlerin, a polyphenolic compound, has been demonstrated to exhibit antitumor activity in various types of human cancer. Several studies have revealed that rottlerin exerts its anticancer function through PKC‑dependent and independent pathways. The transcriptional co‑activator with PDZ‑binding motif (TAZ) oncopreotein is an important molecule in regulation of the Hippo pathway in human cancer. The present study investigated whether rottlerin has a tumor suppressive role via inhibiting the expression of TAZ, using cell viability assay, apoptosis and cell cycle analyses, western blot analysis and Tanswell invasion assay. The results demonstrated that rottlerin suppressed cell growth, triggered cell apoptosis and induced cell cycle arrest. In addition, rottlerin inhibited cell migration and invasion in hepatocellular carcinoma (HCC) cells. Mechanistically, the results demonstrated that rottlerin exerted its antitumor activity partly through the inhibition of TAZ. In addition, the depletion of TAZ led to inhibited cell growth and invasion, whereas the overexpression of TAZ enhanced cell growth and invasion in the HCC cells. Taken together, these findings indicated that the inhibition of TAZ by rottlerin may be a novel strategy for treating HCC.

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“…The NAG-1 expression is modulated at various levels, including transcriptional and post-transcriptional regulation [21]. Rottlerin, a selective inhibitor of the novel isoforms of protein kinase C δ (PKC δ), significantly induced DDIT3 and NAG-1 expression in HT26 colon carcinoma, but DDIT3 siRNA did not affect rottlerin-induced NAG-1 expression [22]. …”

Section: Discussionmentioning

confidence: 99%

Isochaihulactone-induced DDIT3 causes ER stress-PERK independent apoptosis in glioblastoma multiforme cells

Tsai

Tao

et al. 2016

Oncotarget

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The endoplasmic reticulum (ER) is a major site of cellular homeostasis regulation. Under the ER stress condition, Glioblastoma multiform (GBM) cells activate the unfolded protein response. In this study, we discovered isochaihulactone, a natural compound extracted from the Chinese traditional herb Nan-Chai-Hu, which can disrupt ER homeostasis in GBM cell lines. It can induce DNA damage inducible transcript 3 (DDIT3) expression which is independent of 78 kDa glucose-regulated protein (GRP78) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) expression. Flow cytometry results revealed that isochaihulactone trigger the cell cycle arrest at G2/M phase and apoptosis in GBM cells. Isochaihulactone induced DDIT3 led to the expression of NAG-1. The in vivo study showed that isochaihulactone suppressed tumor growth, and DDIT3 and Caspase3 overexpressed in the xenograft model, which is consistent with the in vitro study. Overall, the data revealed that isochaihulactone disrupted ER homeostasis in cancer cells by increasing DDIT3 and NAG-1 expression. Our finding also provides a therapeutic strategy by using isochaihulactone for GBM treatment.

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Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC δ-independent mechanism

Cited by 23 publications

References 26 publications

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

The oncogeneEVI1enhances transcriptional and biological responses of human myeloid cells toall-transretinoic acid

Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma

Isochaihulactone-induced DDIT3 causes ER stress-PERK independent apoptosis in glioblastoma multiforme cells

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