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 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.

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.

scholarly journals MiR-203a-3p Inhibits Pancreatic Cancer Cell Proliferation, EMT, and Apoptosis by Regulating SLUG

2020 ◽  
Vol 19 ◽  
pp. 153303381989872 ◽  
Author(s):  
Ning An ◽  
Bo Zheng
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Messenger Rnas ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

Objective: The aim of the present research is to study the roles of miR-203a-3p on cell proliferation, migration, invasion, and epithelial–mesenchymal transition in pancreatic cancer. Methods: Transcription profiles were acquired from Gene Expression Omnibus database, which was used to screen out the differentially expressed microRNAs and messenger RNAs in pancreatic cancer. Pancreatic cancer tissues were used to verify the bioinformatics results by quantitative real-time polymerase chain reaction. The relationship between miR-203a-3p and SLUG was examined by TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation. The Cell Counting Kit-8, wound healing, and transwell assays were conducted to investigate the proliferation, migration, and invasion capability of pancreatic cancer cells, respectively. The expression of epithelial–mesenchymal transition–related proteins was determined by the Western blot assay. Xenograft assay was performed to verify findings from in vitro assays. Results: Bioinformatic analysis found that a total of 113 microRNAs and 1749 messenger RNAs expressed differentially in pancreatic cancer tissues. Among these microRNAs, the expression of miR-203a-3p was significantly decreased in both pancreatic cancer tissues and cells. On the other hand, the SLUG expression was remarkably upregulated in pancreatic cancer tissues and cells in comparison with normal tissues and cells. Moreover, TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation revealed that SLUG was a target of miR-203a-3p. The upregulation of miR-203a-3p expression inhibited the proliferation, migration, and invasion ability of pancreatic cancer cells by suppressing the epithelial–mesenchymal transition process via sponging SLUG. Conclusion: These findings indicate that downregulation of miR-203a-3p in pancreatic cancer cells leads to high expression of SLUG, which promotes epithelial–mesenchymal transition process and induces cancer progression.

scholarly journals ALKBH5 Inhibits Pancreatic Cancer Motility by Decreasing Long Non-Coding RNA KCNK15-AS1 Methylation

2018 ◽  
Vol 48 (2) ◽  
pp. 838-846 ◽  
Author(s):  
Yuan He ◽  
Hao Hu ◽  
Yandong Wang ◽  
Hao Yuan ◽  
Zipeng Lu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
The Body ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cancer Pathogenesis ◽  
Non Coding Rna ◽  
Cancer Tissues ◽  
Long Non Coding Rna

Background/Aims: Mounting evidence suggests that epitranscriptional modifications regulate multiple cellular processes. N6-Methyladenosine (m6A), the most abundant reversible methylation of mRNA, has critical roles in cancer pathogenesis. However, the mechanisms and functions of long non-coding RNA (lncRNA) methylation remain unclear. Pancreatic cancer resulted in 411,600 deaths globally in 2015. By the time of pancreatic cancer diagnosis, metastasis has often occurred in other parts of the body. The present study sought to investigate lncRNA m6A modification and its roles in pancreatic cancer. Methods: Differential expression between cancer cells and matched normal cells was evaluated to identify candidate lncRNAs. The lncRNA KCNK15-AS1 was detected in cancer tissues and various pancreatic cells using RT-qPCR. KCNK15-AS1 was transfected into cells to explore its role in migration and invasion. Then, m6A RNA immunoprecipitation was performed to detect methylated KCNK15-AS1 in tissues and cells. Epithelial–mesenchymal transition (EMT) markers were used to evaluate KCNK15-AS1-mediated EMT processes. Results: KCNK15-AS1 was downregulated in pancreatic cancer tissues compared with paired adjacent normal tissues. KCNK15-AS1 inhibited migration and invasion in MIA PaCa-2 and BxPC-3 cells. Furthermore, total RNA methylation in cancer cells was significantly enriched relative to that in immortalized human pancreatic duct epithelial (HPDE6-C7) cells. In addition, the m6A eraser ALKBH5 was downregulated in cancer cells, which can demethylate KCNK15-AS1 and regulate KCNK15-AS1-mediated cell motility. Conclusion: Our results have revealed a novel mechanism by which ALKBH5 inhibits pancreatic cancer motility by demethylating lncRNA KCNK15-AS1, identifying a potential therapeutic target for pancreatic cancer.

scholarly journals Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial–Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1856 ◽  
Author(s):  
Wei ◽  
Penso ◽  
Hackman ◽  
Wang ◽  
Mackenzie
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cancer Cell Growth ◽  
Mesenchymal Transition

Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer cell migration and invasion and the underlying mechanisms. EGCG reduced pancreatic cancer cell growth, migration, and invasion in vitro and in vivo. EGCG prevented “Cadherin switch” and decreased the expression level of TCF8/ZEB1, β-Catenin, and Vimentin. Mechanistically, EGCG inhibited the Akt pathway in a time-dependent manner, by suppressing IGFR phosphorylation and inducing Akt degradation. Co-treatment with catalase or N-Acetyl-L-cysteine did not abrogate EGCG’s effect on the Akt pathway or cell growth. Moreover, EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial–mesenchymal transition markers and inhibiting Akt pathway. In summary, EGCG may prove beneficial to improve gemcitabine sensitivity in inhibiting pancreatic cancer cell migration and invasion, to some extent through the inhibition of Akt pathway and epithelial–mesenchymal transition.

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