Sulforaphane as New Therapeutic Agent for Targeting of Cancer Stem Cells with Focus to Prostate and Pancreatic Cancer

2012 ◽  
pp. 27-32
Author(s):  
Ingrid Herr ◽  
Vanessa Rausch
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Agent

scholarly journals Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudia Di Carlo ◽  
Bebiana C. Sousa ◽  
Marcello Manfredi ◽  
Jessica Brandi ◽  
Elisa Dalla Pozza ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Fatty Acid ◽  
Cancer Stem Cells ◽  
Acyl Chain ◽  
Fatty Acid Elongase ◽  
Acyl Chains ◽  
A Chain ◽  
Pancreatic Cancer Stem Cells ◽  
Long Chain

AbstractPancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha. The upregulated proteins of PCSCs are mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics reveals an increase in long and very long-chain unsaturated FAs, which are products of fatty acid elongase-5 predicted as a key gene. Moreover, lipidomics showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of FA elongation and alteration in cardiolipin acyl chain composition in PCSCs, representing attractive therapeutic targets in PDAC.

scholarly journals The plasticity of pancreatic cancer stem cells: implications in therapeutic resistance

2021 ◽  
Author(s):  
Kalyani Patil ◽  
Farheen B. Khan ◽  
Sabah Akhtar ◽  
Aamir Ahmad ◽  
Shahab Uddin
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Disease Recurrence ◽  
Resistance Mechanisms ◽  
Cytotoxic Agents ◽  
Plastic State ◽  
Metastatic Progression ◽  
Acquired Drug Resistance ◽  
Natural Agents

AbstractThe ever-growing perception of cancer stem cells (CSCs) as a plastic state rather than a hardwired defined entity has evolved our understanding of the functional and biological plasticity of these elusive components in malignancies. Pancreatic cancer (PC), based on its biological features and clinical evolution, is a prototypical example of a CSC-driven disease. Since the discovery of pancreatic CSCs (PCSCs) in 2007, evidence has unraveled their control over many facets of the natural history of PC, including primary tumor growth, metastatic progression, disease recurrence, and acquired drug resistance. Consequently, the current near-ubiquitous treatment regimens for PC using aggressive cytotoxic agents, aimed at ‘‘tumor debulking’’ rather than eradication of CSCs, have proven ineffective in providing clinically convincing improvements in patients with this dreadful disease. Herein, we review the key hallmarks as well as the intrinsic and extrinsic resistance mechanisms of CSCs that mediate treatment failure in PC and enlist the potential CSC-targeting ‘natural agents’ that are gaining popularity in recent years. A better understanding of the molecular and functional landscape of PCSC-intrinsic evasion of chemotherapeutic drugs offers a facile opportunity for treating PC, an intractable cancer with a grim prognosis and in dire need of effective therapeutic advances.

scholarly journals PAWI-2 overcomes tumor stemness and drug resistance via cell cycle arrest in integrin β3-KRAS-dependent pancreatic cancer stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiongjia Cheng ◽  
John R. Cashman
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Cycle Arrest ◽  
Specific Inhibitor ◽  
Feedback Mechanism ◽  
Major Health Problem ◽  
Cycle Arrest ◽  
Drug Inhibition

Abstract Today, pancreatic cancer (PC) remains a major health problem in the US. The fact that cancer stem cells (CSCs) become enriched in humans following anti-cancer therapy implicates CSCs as key contributors to tumor dormancy, metastasis, and relapse in PC. A highly validated CSC model (FGβ3 cells) was used to test a novel compound (PAWI-2) to eradicate CSCs. Compared to parental bulk FG cells, PAWI-2 showed greater potency to inhibit cell viability and self-renewal capacity of FGβ3 cells. For FGβ3 cells, dysregulated integrin β3-KRAS signaling drives tumor progression. PAWI-2 inhibited β3-KRAS signaling independent of KRAS. This is clinically relevant. PAWI-2 targeted the downstream TBK1 phosphorylation cascade that was negatively regulated by optineurin phosphorylation via a feedback mechanism. This was confirmed by TBK1 genetic knockdown or co-treatment with TBK1-specific inhibitor (MRT67307). PAWI-2 also overcame erlotinib (an EGFR inhibitor) resistance in FGβ3 cells more potently than bortezomib. In the proposed working model, optineurin acts as a key regulator to link inhibition of KRAS signaling and cell cycle arrest (G2/M). The findings show PAWI-2 is a new approach to reverse tumor stemness that resensitizes CSC tumors to drug inhibition.

206 Identification and Whole Transcriptome Characterization of Pancreatic Cancer Stem Cells

2012 ◽  
Vol 142 (5) ◽  
pp. S-50-S-51
Author(s):  
Christina Vorvis ◽  
George A. Poultsides ◽  
Jeffrey A. Norton ◽  
Maria Hatziapostolou ◽  
Dimitrios Iliopoulos
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Whole Transcriptome ◽  
Pancreatic Cancer Stem Cells

Targeting pancreatic cancer stem cells for cancer therapy

2012 ◽  
Vol 1826 (2) ◽  
pp. 385-399 ◽  
Author(s):  
Jun Xia ◽  
Changjie Chen ◽  
Zhiwen Chen ◽  
Lucio Miele ◽  
Fazlul H. Sarkar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Pancreatic Cancer Stem Cells

PS02.061: TRANILAST: SPECIFIC INHIBITOR OF TRPV2 IS THERAPEUTIC AGENT OF ESOPHAGEAL CANCER STEM CELLS

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 138-138
Author(s):  
Keita Katsurahara ◽  
Atsushi Shiozaki ◽  
Michihiro Kudou ◽  
Katsutoshi Shoda ◽  
Tomohiro Arita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Membrane Proteins ◽  
Cancer Stem Cells ◽  
Microarray Analysis ◽  
Therapeutic Agent ◽  
Transient Receptor Potential ◽  
Conflicts Of Interest ◽  
Expression Profiles ◽  
Specific Inhibitor

Abstract Background Recent studies revealed that membrane proteins, such as ion transporters, are specifically activated in cancer stem cells (CSCs). Therefore, these molecules are receiving a great attention as new chemotherapeutic targets of malignant tumor. This study aimed to investigate the expression and activity of ion transport-related molecules in CSCs of esophageal squamous cell carcinoma (ESCC). Methods We sorted cells with high expression of ALDH1A1 via FACS, and then, CSCs were generated using the sphere formation assay. The gene expression profiles of CSCs were examined using a microarray analysis. Candidate genes of membrane proteins activated in CSCs were selected based on that microarray data. Anticancer effects induced by inhibition of the selected proteins were examined. Results ALDH1A1 mRNA and protein levels were certainly upregulated in CSCs compared with non-CSCs. Obtained CSCs were resistant to Cisplatin and had the ability of re-differentiation. The results of the microarray analysis revealed that expressions of 50 genes of plasma membrane proteins were changed in CSCs, and that several genes related to ion channels, including transient receptor potential cation channel subfamily V member 2 (TRPV2), were upregulated. The upregulation of TRPV2 mRNA were also validated in CSCs derived from two types of esophageal cancer cell lines using RT-PCR method. Tranilast, which is specific TRPV2 inhibitor, was more cytotoxic at lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. Further, Tranilast significantly decreased the cell population with high ALDH1A1 expression in esophageal cancer cells. Conclusion The results of the present study suggest that TRPV2 is involved in the maintenance of CSCs, and Tranilast, which is specific inhibitor of TRPV2, becomes a promising targeted therapeutic agent against ESCC. Disclosure All authors have declared no conflicts of interest.

scholarly journals Long noncoding RNA LINC00261 upregulates ITIH5 to impair tumorigenic ability of pancreatic cancer stem cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Lijuan Zou ◽  
Hengpeng He ◽  
Zhiguo Li ◽  
Ou Chen ◽  
Xiukun Jia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Noncoding Rna ◽  
Cell Subset ◽  
Luciferase Reporter ◽  
Stem Cell Markers ◽  
Self Renewal

AbstractLong noncoding RNAs (lncRNAs) are implicated tumor development in a range of different cancers, including pancreatic cancer (PC). Cancer stem cells (CSCs), a drug-resistant cancer cell subset, drive tumor progression in PC. In this work, we aimed to investigate the mechanism by which lncRNA LINC00261 affects the biological functions of CSCs during the progression of PC. Microarray analysis of differentially expressed genes and lncRNAs suggested that LINC00261 is downregulated in PC. Both LINC00261 and ITIH5 were confirmed to be downregulated in PC cells and PC stem cells. Gain-of-function and loss-of-function investigations were performed to analyze their effects on cell proliferation, drug resistance, cell cycle distribution, self-renewal, invasion, and ultimately overall tumorigenicity. These experiments revealed that the expression of stem cell markers was reduced, and cell proliferation, self-renewal ability, cell invasion, drug resistance, and tumorigenicity were all suppressed by upregulation of LINC00261 or ITIH5. The results of dual-luciferase reporter gene, ChIP, and RIP assays indicated that LINC00261 binds directly to GATA6, increasing its activity at the ITIH5 promoter. The presence of LINC00261 and GATA6 inhibited the self-renewal and tumorigenesis of PC stem cells, while silence of ITIH5 rescued those functions. Collectively, this study identifies the tumor suppressive activity of LINC00261 in PC, showing that this lncRNA limits the functions of PC stem through an ITIH5/GATA6 regulatory pathway.

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