scholarly journals Caffeic Acid Phenethyl Ester Inhibits Epithelial-Mesenchymal Transition of Human Pancreatic Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ming-Jen Chen ◽  
Shou-Chuan Shih ◽  
Horng-Yuan Wang ◽  
Ching-Chung Lin ◽  
Chia-Yuan Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Caffeic Acid ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Caffeic Acid Phenethyl Ester ◽  
Human Pancreatic Cancer ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Migration Potential

Background. This study aimed to investigate the effect of propolis component caffeic acid phenethyl ester (CAPE) on epithelial-mesenchymal transition (EMT) of human pancreatic cancer cells and the molecular mechanisms underlying these effects.Methods. The transforming growth factorβ(TGF-β-) induced EMT in human pancreatic PANC-1 cancer cells was characterized by observation of morphology and the expression of E-cadherin and vimentin by western blotting. The migration potential was estimated with wound closure assay. The expression of transcriptional factors was measured by quantitative RT-PCR and immunocytochemistry staining. The orthotopic pancreatic cancer xenograft model was used forin vivoassessment.Results. The overexpression of vimentin was attenuated by CAPE, and the alteration in morphology from polygonal to spindle shape was partially reversed by CAPE. Furthermore, CAPE delayed the TGF-β-stimulated migration potential. CAPE treatment did not reduce the expression levels of Smad 2/3, Snail 1, and Zeb 1 but inhibited the expression of transcriptional factor Twist 2. By using an orthotopic pancreatic cancer model, CAPE suppressed the expression of Twist 2 and growth of PANC-1 xenografts without significant toxicity.Conclusion. CAPE could inhibit the orthotopic growth and EMT of pancreatic cancer PANC-1 cells accompanied by downregulation of vimentin and Twist 2 expression.

Caffeic Acid Phenethyl Ester Induces Apoptosis of Human Pancreatic Cancer Cells Involving Caspase and Mitochondrial Dysfunction

Pancreatology ◽  
2008 ◽  
Vol 8 (6) ◽  
pp. 558-565 ◽  
Author(s):  
Ming-Jen Chen ◽  
Wen-Hsiung Chang ◽  
Ching-Chung Lin ◽  
Chia-Yuan Liu ◽  
Tsang-En Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Caffeic Acid ◽  
Caffeic Acid Phenethyl Ester ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals α-Mangostin Suppresses the Viability and Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells by Downregulating the PI3K/Akt Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Qinhong Xu ◽  
Jiguang Ma ◽  
Jianjun Lei ◽  
Wanxing Duan ◽  
Liang Sheng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Complementary Alternative Medicine ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Matrigel Invasion ◽  
Pancreatic Cancer Cells

α-Mangostin, a natural product isolated from the pericarp of the mangosteen fruit, has been shown to inhibit the growth of tumor cells in various types of cancers. However, the underlying molecular mechanisms are largely unclear. Here, we report thatα-mangostin suppressed the viability and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells through inhibition of the PI3K/Akt pathway. Treatment of pancreatic cancer BxPc-3 and Panc-1 cells withα-mangostin resulted in loss of cell viability, accompanied by enhanced cell apoptosis, cell cycle arrest at G1 phase, and decrease of cyclin-D1. Moreover, Transwell and Matrigel invasion assays showed thatα-mangostin significantly reduced the migration and invasion of pancreatic cancer cells. Consistent with these results,α-mangostin decreased the expression of MMP-2, MMP-9, N-cadherin, and vimentin and increased the expression of E-cadherin. Furthermore, we found thatα-mangostin suppressed the activity of the PI3K/Akt pathway in pancreatic cancer cells as demonstrated by the reduction of the Akt phosphorylation byα-mangostin. Finally,α-mangostin significantly inhibited the growth of BxPc-3 tumor mouse xenografts. Our results suggest thatα-mangostin may be potentially used as a novel adjuvant therapy or complementary alternative medicine for the management of pancreatic cancers.

scholarly journals HMGA2 Maintains Oncogenic RAS-Induced Epithelial-Mesenchymal Transition in Human Pancreatic Cancer Cells

2009 ◽  
Vol 174 (3) ◽  
pp. 854-868 ◽  
Author(s):  
Sugiko Watanabe ◽  
Yasuaki Ueda ◽  
Shin-ichi Akaboshi ◽  
Yuko Hino ◽  
Yoko Sekita ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Pancreatic Cancer ◽  
Mesenchymal Transition ◽  
Oncogenic Ras ◽  
Pancreatic Cancer Cells

scholarly journals Mint3 depletion restricts tumor malignancy of pancreatic cancer cells by decreasing SKP2 expression via HIF-1

Oncogene ◽  
2020 ◽  
Vol 39 (39) ◽  
pp. 6218-6230 ◽  
Author(s):  
Akane Kanamori ◽  
Daisuke Matsubara ◽  
Yurika Saitoh ◽  
Yuya Fukui ◽  
Noriko Gotoh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Human Pancreatic Cancer ◽  
Mesenchymal Transition ◽  
Skp2 Expression ◽  
Pancreatic Cancer Cells

Abstract Pancreatic cancer is one of the most fatal cancers without druggable molecular targets. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcriptional factor that promotes malignancy in various cancers including pancreatic cancer. Herein, we found that HIF-1 is accumulated in normoxic or moderate hypoxic areas of pancreatic cancer xenografts in vivo and is active even during normoxia in pancreatic cancer cells in vitro. This prompted us to analyze whether the HIF-1 activator Mint3 contributes to malignant features of pancreatic cancer. Mint3 depletion by shRNAs attenuated HIF-1 activity during normoxia and cell proliferation concomitantly with accumulated p21 and p27 protein in pancreatic cancer cells. Further analyses revealed that Mint3 increased transcription of the oncogenic ubiquitin ligase SKP2 in pancreatic cancer cells via HIF-1. This Mint3-HIF-1-SKP2 axis also promoted partial epithelial-mesenchymal transition, stemness features, and chemoresistance in pancreatic cancer cells. Even in vivo, Mint3 depletion attenuated tumor growth of orthotopically inoculated human pancreatic cancer AsPC-1 cells. Database and tissue microarray analyses showed that Mint3 expression is correlated with SKP2 expression in human pancreatic cancer specimens and high Mint3 expression is correlated with poor prognosis of pancreatic cancer patients. Thus, targeting Mint3 may be useful for attenuating the malignant features of pancreatic cancer.

scholarly journals Oncogenic K-ras Induces Mitochondrial OPA3 Expression to Promote Energy Metabolism in Pancreatic Cancer Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 65 ◽  
Author(s):  
Ning Meng ◽  
Christophe Glorieux ◽  
Yanyu Zhang ◽  
Liyun Liang ◽  
Peiting Zeng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Energy Metabolism ◽  
Cancer Cells ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Negative Impact ◽  
Human Embryonic Kidney Cells ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

K-ras (Kirsten ras GTPase) mutations are oncogenic events frequently observed in many cancer types especially in pancreatic cancer. Although mitochondrial dysfunction has been associated with K-ras mutation, the molecular mechanisms by which K-ras impacts mitochondria and maintains metabolic homeostasis are not fully understood. In this study, we used two K-ras inducible cell systems, human pancreatic epithelial/ K-rasG12D (HPNE/K-rasG12D) and human embryonic kidney cells with tetracycline repressorT-Rex/K-rasG12V, to evaluate the role of oncogenic K-ras in regulating mitochondrial function. Among a panel of genes known to affect mitochondria, only the expression of OPA3 (optic atrophy protein 3) was consistently up-regulated by K-ras activation in both cell lines. Importantly, high expression of OPA3 was also observed in clinical pancreatic cancer tissues. Genetic knockdown of OPA3 caused a significant decrease of energy metabolism, manifested by a suppression of oxygen consumption rate (OCR) and a decrease in cellular ATP content, leading to inhibition of cell proliferation capacity and reduced expression of epithelial–mesenchymal transition (EMT) markers. Our study suggests that OPA3 may promote cellular energy metabolism and its up-regulation in K-ras-driven cancer is likely a mechanism to offset the negative impact of K-ras on mitochondria to maintain energy homeostasis. As such, OPA3 could be a potential target to kill cancer cells with K-ras mutations.

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