Development of Cerium Oxide Nanoparticles and Its Cytotoxicity in Prostate Cancer Cells

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.

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Targeting and Cellular Trafficking of Magnetic Nanoparticles for Prostate Cancer Imaging

Molecular Imaging ◽

10.2310/7290.2007.00025 ◽

2007 ◽

Vol 6 (4) ◽

pp. 7290.2007.00025 ◽

Cited By ~ 44

Author(s):

Rita E. Serda ◽

Natalie L. Adolphi ◽

Marco Bisoffi ◽

Laurel O. Sillerud

Keyword(s):

Prostate Cancer ◽

Iron Oxide ◽

Cancer Cells ◽

Iron Oxide Nanoparticles ◽

Magnetic Particles ◽

Metastatic Cancer ◽

Confocal Laser ◽

Oxide Nanoparticles ◽

Prostate Cancer Cells ◽

Mr Images

Antibody-conjugated iron oxide nanoparticles offer a specific and sensitive tool to enhance magnetic resonance (MR) images of both local and metastatic cancer. Prostate-specific membrane antigen (PSMA) is predominantly expressed on the neovasculature of solid tumors and on the surface of prostate cells, with enhanced expression following androgen deprivation therapy. Biotinylated anti-PSMA antibody was conjugated to streptavidin-labeled iron oxide nanoparticles and used in MR imaging and confocal laser scanning microscopic imaging studies using LNCaP prostate cancer cells. Labeled iron oxide nanoparticles are internalized by receptor-mediated endocytosis, which involves the formation of clathrin-coated vesicles. Endocytosed particles are not targeted to the Golgi apparatus for recycling but instead accumulate within lysosomes. In T1-weighted MR images, the signal enhancement owing to the magnetic particles was greater for cells with magnetic particles bound to the cell surface than for cells that internalized the particles. However, the location of the particles (surface vs internal) did not significantly alter their effect on T2-weighted images. Our findings indicate that targeting prostate cancer cells using PSMA offers a specific and sensitive technique for enhancing MR images.

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The Expression of Antioxidant Genes and Cytotoxicity of Biosynthesized Cerium Oxide Nanoparticles Against Hepatic Carcinoma Cell Line

Avicenna Journal of Medical Biochemistry ◽

10.34172/ajmb.2019.04 ◽

2019 ◽

Vol 7 (1) ◽

pp. 16-20 ◽

Cited By ~ 3

Author(s):

Ali Es-haghi ◽

Fatemeh Javadi ◽

Mohammad Ehsan Taghavizadeh Yazdi ◽

Mohammad Sadegh Amiri

Keyword(s):

Cancer Cells ◽

Cell Line ◽

Cerium Oxide ◽

Carcinoma Cell ◽

Cerium Oxide Nanoparticles ◽

Oxide Nanoparticles ◽

Hepatic Carcinoma ◽

Normal Cells ◽

Antioxidant Genes ◽

Cancerous Cells

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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