scholarly journals A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

2012 ◽  
Vol 263 (2) ◽  
pp. 225-232 ◽  
Author(s):  
Kyung-Won Min ◽  
Xiaobo Zhang ◽  
Temjenmongla Imchen ◽  
Seung Joon Baek
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Proliferative Response ◽  
Peroxisome Proliferator ◽  
Receptor Ligand ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pancreatic Cancer Cells

Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cancer cells through the reduction of cyclin D1

Life Sciences ◽  
2002 ◽  
Vol 70 (13) ◽  
pp. 1565-1575 ◽  
Author(s):  
Miyuki Toyota ◽  
Yoshiji Miyazaki ◽  
Shinji Kitamura ◽  
Yutaka Nagasawa ◽  
Tatsuya Kiyohara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Rate ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pancreatic Cancer Cells

Targeted pancreatic cancer drug-delivery utilizing sigma-2 ligand/receptor internalization is energy-dependent.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 331-331
Author(s):  
Linda X Jin ◽  
Suwanna Vangveravong ◽  
Darren R Cullinan ◽  
Peter S. Goedegebuure ◽  
Andrew J Loza ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Drug ◽  
Receptor Ligands ◽  
Ligand Interaction ◽  
Receptor Ligand ◽  
Pancreatic Cancer Cells ◽  
Cancer Drug Delivery ◽  
Energy Dependent

331 Background: Pancreatic cancer is a devastating disease that is poorly responsive to traditional systemic therapies. Cancer-selective drug delivery can improve survival and reduce systemic toxicities. We have developed a pancreatic cancer drug delivery platform based on sigma-2 receptor ligands conjugated to small molecule drug cargos, which improves delivery and efficacy through efficient drug internalization. However, the mechanism of drug internalization via the sigma-2 receptor/ligand interaction remains unclear. Methods: Uptake of fluorescently conjugated sigma-2 ligand SW120 was studied in ASPC-1 human pancreatic cancer cells. Uptake was measured at 37C, 4C, after competitive inhibition with sigma-2 ligand SW43, and after pretreatment with Pitstop 2 (Abcam), an inhibiter of clathrin-mediated endocytosis. Uptake was visualized using live-cell imaging using A1Rsi confocal laser scanning microscope (Nikon). Image analysis was performed using FIJI (NIH) and Matlab (Mathworks). Results: SW120 (10 nM) was rapidly internalized into ASPC-1 cells at 37C with maximal fluorescence at 12 minutes. As a negative control, incubation of ASPC-1 cells with the unconjugated flourophore NBD Cl demonstrated no uptake after 15 minutes, indicating that uptake of SW120 depends on the specific sigma-2 receptor/ligand interaction. Fluorescence at 15 minutes was reduced by 85% in ASPC-1 cells incubated at 4C, indicating uptake of SW120 into cells is an energy dependent process. Pretreatment of cells with Pitstop 2 decreased total flourescence at 15 minutes by 76%, suggesting an important role of clathrin-mediated endocytosis in sigma-2 receptor uptake, while pretreatment with competitive inhibitor SW43 reduced uptake by 84%, suggesting that sigma-2 ligands are internalized via a specific receptor capable of saturation. Conclusions: Sigma-2 receptor ligands are rapidly internalized into pancreatic cancer cells via a specific, targetable, energy-dependent pathway that appears to rely on clathrin-mediated endocytosis. Further understanding of sigma-2 mediated drug internalization can help optimize targeted drug development and delivery for pancreatic cancer patients.

scholarly journals Role of Peroxisome Proliferator-Activated Receptorβ/δand B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jeffrey D. Coleman ◽  
Jerry T. Thompson ◽  
Russell W. Smith ◽  
Bogdan Prokopczyk ◽  
John P. Vanden Heuvel
Keyword(s):  
Pancreatic Cancer ◽  
Basement Membrane ◽  
Cancer Cells ◽  
Target Genes ◽  
B Cell Lymphoma ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Peroxisome Proliferator ◽  
Matrix Remodeling ◽  
Pancreatic Cancer Cells

PPARβ/δis a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor,BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis thatPPARβ/δis expressed in human pancreatic cancer cells and that its activation could regulateMMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression ofMMP-9andPPARβ/δ, and lower levels ofBCL-6mRNA.PPARβ/δactivation reduced the TNFα-induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors ofPPARβ/δ,BCL-6, andMMP-9, it was evident thatPPARβ/δwas responsible for the ligand-dependent effects whereasBCL-6dissociation upon GW501516 treatment was ultimately responsible for decreasingMMP-9expression and hence invasion activity. These results suggest thatPPARβ/δplays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release ofBCL-6and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.

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