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 ◽  
...  

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.

2013 ◽  
Vol 9 (4) ◽  
pp. 558-569 ◽  
Author(s):  
Melissa S. Wason ◽  
Jimmie Colon ◽  
Soumen Das ◽  
Sudipta Seal ◽  
James Turkson ◽  
...  

2016 ◽  
Vol 43 (6Part37) ◽  
pp. 3784-3784
Author(s):  
Z Ouyang ◽  
S Yasmin-Karim ◽  
G Strack ◽  
E Sajo ◽  
W Ngwa

2012 ◽  
Vol 6 (1) ◽  
pp. 17-25 ◽  
Author(s):  
G. Renu ◽  
V. V. Divya Rani ◽  
S. V. Nair ◽  
K. R. V. Subramanian ◽  
Vinoth-Kumar Lakshmanan

2015 ◽  
Author(s):  
Venugopal Gunda ◽  
Jaime Abrego ◽  
Surendra K. Shukla ◽  
Nina V. Chaika ◽  
Fang Yu ◽  
...  

Author(s):  
Jorge A Roacho-Pérez ◽  
Elsa N Garza-Treviño ◽  
Paulina Delgado-Gonzalez ◽  
Zuca G-Buentello ◽  
Juan Luis Delgado-Gallegos ◽  
...  

Pancreatic cancer leads the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve a non-specific use of chemotherapeutical agents like 5-FU, capecitabine, gemcitabine, cisplatine, oxaliplatine, or irinotecan, that produce several side effects. This review we focus on the use of targeted nanoparticles as an alternative to the standard treatment for the pancreatic cancer. The principal objective of the use of nanoparticles is the reduction in side effects that conventional treatments produce, mostly because of their nonspecificity. Currently, several molecular markets of pancreatic cancer cells have been studied to target nanoparticles and improve the actual treatment. Therefore, properly functionalizated nanoparticles with specific aptamers or antibodies can be used to recognize pancreatic cancer cells and once cancer is recognized, these nanoparticles can attack the tumor by drug delivery, hyperthermia, or gene therapy.


2018 ◽  
Author(s):  
R. A. Vazirov ◽  
S. Y. Sokovnin ◽  
V. G. Ilves ◽  
A. V. Myshkina ◽  
I. N. Bazhukova

2019 ◽  
Vol 7 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Ali Es-haghi ◽  
Fatemeh Javadi ◽  
Mohammad Ehsan Taghavizadeh Yazdi ◽  
Mohammad Sadegh Amiri

Background: Drug resistance due to genetic variations renders many therapeutic methods such as surgery, radiotherapy, chemotherapy, and hormone therapy unsuccessful in eradicating cancerous cells. Nowadays, application of nanoparticles (NPs) has been promising in destroying cancerous cells without side effects on normal cells. Objectives: This study aimed to investigate the antioxidant and anticancer effects of biosynthesized cerium oxide nanoparticles (CeO2 -NPs) on a hepatic carcinoma cell line. Methods: MTT assay was used to determine the cytotoxicity of CeO2 -NPs in concentrations of 0, 15.6, 31.2, 62.5, 125, and 250 μg/mL after 24, 48, and 72 hours of incubation. Moreover, the expression levels of catalase (CAT) and superoxide dismutase (SOD) (the antioxidant genes) were investigated at different concentrations of CeO2 -NPs using real-time polymerase chain reaction (PCR). Results: Our results showed a significant toxicity of the synthesized NPs against the cancerous liver cells. The IC50 calculated for CeO2 -NPs was 500 μg/mL at 24 hours of incubation. In addition, the expression levels of CAT and SOD significantly (P<0.05) increased upon the treatment of cells with CeO2 -NPs (500 µg /mL) compared to the untreated cells. Conclusion: Considering the minimal effects of the biosynthesized CeO2 -NPs on normal cells and on the other hand their considerable toxicity against hepatic cancer cells, these NPs could be utilized in medicine and in the development of new drugs for cancer cells.


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