scholarly journals Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production

2013 ◽  
Vol 9 (4) ◽  
pp. 558-569 ◽  
Author(s):  
Melissa S. Wason ◽  
Jimmie Colon ◽  
Soumen Das ◽  
Sudipta Seal ◽  
James Turkson ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cerium Oxide ◽  
Ros Production ◽  
Pancreatic Cancer Cells ◽  
Oxide Nanoparticle

scholarly journals Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer to Radiation Therapy through Oxidative Activation of the JNK Apoptotic Pathway

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 303 ◽  
Author(s):  
Melissa Wason ◽  
Heng Lu ◽  
Lin Yu ◽  
Satadru Lahiri ◽  
Debarati Mukherjee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Side Effects ◽  
Cancer Cells ◽  
Cerium Oxide ◽  
Mitotic Catastrophe ◽  
Cerium Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Pancreatic Cancer Cells ◽  
Jnk Activation

Side effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. Cerium oxide nanoparticles (CONPs) are currently being tested in pre-clinical trials as an adjuvant to sensitize pancreatic cancer cells to RT and protect normal tissues from the harmful side effects. CONPs were not able to significantly affect RT-induced DNA damage in cancer cells, thereby ruling out sensitization through increased mitotic catastrophe. However, activation of c-Jun terminal kinase (JNK), a key driver of RT-induced apoptosis, was significantly enhanced by co-treatment with CONPs and RT in pancreatic cancer cells in vitro and human pancreatic tumors in nude mice in vivo compared to CONPs or RT treatment alone. Further, CONP-driven increase in RT-induced JNK activity was associated with a marked increase in Caspase 3/7 activation, indicative of apoptosis. We have previously shown that CONPs increase reactive oxygen species (ROS) production in cancer cells. ROS has been shown to drive the oxidation of thioredoxin 1 (TRX1) which results in the activation of apoptosis signaling kinase 1 (ASK1). The increase in ASK1 activation following the co-treatment with CONPs followed by RT suggests that the increased JNK activation is the result of increased TRX1 oxidation. The ability of CONPs to sensitize pancreatic cancer cells to RT was mitigated when the TRX1 oxidation was prevented by mutagenesis of a cysteine residue or when the JNK activation was blocked by an inhibitor. Taken together, these data demonstrate an important mechanism for CONPs in specifically killing cancer cells and provide novel insights into the utilization of CONPs as a radiosensitizer and therapeutic agent for pancreatic cancer.

Non-mitochondrial NAD(P)H oxidase mediates growth factor-induced ROS production and suppression of apoptosis in pancreatic cancer cells

2003 ◽  
Vol 124 (4) ◽  
pp. A290 ◽  
Author(s):  
Eva C. Vaquero ◽  
Kyung J. Nam ◽  
Ilya Gukovsky ◽  
Stephen J. Pandol ◽  
Anna S. Gukovskaya
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Ros Production ◽  
Pancreatic Cancer Cells

The Radio-Sensitizing Effect of Pharmacological Concentration of Ascorbic Acid on Human Pancreatic Cancer Cells

2020 ◽  
Vol 20 (16) ◽  
pp. 1927-1932
Author(s):  
Dian Dayer ◽  
Mohammad R. Tabandeh ◽  
Majid Kazemi
Keyword(s):  
Pancreatic Cancer ◽  
Ascorbic Acid ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Dna Fragmentation ◽  
Human Pancreatic Cancer ◽  
Control Group ◽  
Ros Production ◽  
Pancreatic Cancer Cells

Background: Previous studies reported the inevitable destructive effects of radiotherapy on normal adjacent cells. Ascorbic Acid (AA) has been proposed as an effective anti-cancer agent with no obvious effects on normal cells. Objective: The effects of Ascorbic acid in combination with radiotherapy on human pancreatic carcinoma cell line were studied. Methods: The human pancreatic cancer cells were cultured and divided into four groups: control group (A) without any treatment, group B that received 2Gy radiotherapy alone, group C that was treated with 4mM AA alone, and group D that was co-treated with AA and radiotherapy. Cell viability, DNA fragmentation, expression of apoptotic genes, and Reactive Oxygen Species (ROS) production were determined in treated cells. Results: There was a noticeable decrease in cell viability after treatment with AA (and/or) radiotherapy. All treated groups showed elevated ROS production, Bax/Bcl2 expression, DNA fragmentation, and cytotoxycity compared with the control group. Cells under combination therapy showed the most cytotoxicity. Conclusion: The results suggest that AA at a dose of 4mmol/l may be used as an effective radio-sensitizing agent in pancreatic cancer cell line.

Extracellular matrix stimulates reactive oxygen species production and increases pancreatic cancer cell survival through 5-lipoxygenase and NADPH oxidase

2005 ◽  
Vol 289 (6) ◽  
pp. G1137-G1147 ◽  
Author(s):  
Mouad Edderkaoui ◽  
Peggy Hong ◽  
Eva C. Vaquero ◽  
Jong K. Lee ◽  
Lars Fischer ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Growth Factors ◽  
Nadph Oxidase ◽  
Cancer Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Pancreatic Cancer Cells ◽  
Ecm Proteins

The extracellular matrix (ECM) facilitates pancreatic cancer cells survival, which is of central importance for pancreatic adenocarcinoma that is highly fibrotic. Here, we show that reactive oxygen species (ROS) mediate the prosurvival effect of ECM in human pancreatic cancer cells. Fibronectin and laminin stimulated ROS production and NADPH oxidase activation in pancreatic cancer cells. Both pharmacological and molecular approaches show that fibronectin stimulated ROS production through activation of NADPH oxidase and NADPH oxidase-independent pathways and that 5-lipoxygenase (5-LO) mediates both these pathways. Analyses of the mechanisms of ROS production by ECM proteins and growth factors indicate that activation of NADPH oxidase (Nox4) is a common mechanism employed both by ECM proteins and growth factors to increase ROS in pancreatic cancer cells. We also found that Nox4 is present in human pancreatic adenocarcinoma tissues and that these tissues display membrane NADPH oxidase activity. ECM proteins and growth factors activate NADPH oxidase through different mechanisms; in contrast to ECM proteins, growth factors activate NADPH oxidase through 5-LO-independent mechanisms. Inhibition of 5-LO or NADPH oxidase with pharmacological inhibitors of these enzymes and with Nox4 or 5-LO antisense oligonucleotides markedly stimulated apoptosis in cancer cells cultured on fibronectin. Our results indicate that ROS generation via 5-LO and downstream NADPH oxidase mediates the prosurvival effect of ECM in pancreatic cancer cells. These mechanisms may play an important role in pancreatic cancer resistance to treatments and thus represent novel therapeutic targets.

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