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Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer.

ABSTRACT: Ovarian cancer (OvCa) is the fifth most common cause of death from all cancers among women in United Sates and the leading cause of death from gynecological malignancies. While most OvCa patients initially respond to surgical debulking and chemotherapy, 75% of patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with OvCa. In this context, we have developed and engineered Nanoceria (NCe), nanoparticles of cerium oxide, possessing anti-oxidant properties, to be used as a therapeutic agent in OvCa. We show for the first time that NCe significantly inhibited production of reactive oxygen species (ROS) in A2780 cells, attenuated growth factor (SDF1, HB-EGF, VEGF(165) and HGF) mediated cell migration and invasion of SKOV3 cells, without affecting the cell proliferation. NCe treatment also inhibited VEGF(165) induced proliferation, capillary tube formation, activation of VEGFR2 and MMP2 in human umbilical vascular endothelial cells (HUVEC). NCe (0.1 mg/kg body weigh) treatment of A2780 ovarian cancer cells injected intra-peritoneally in nude mice showed significant reduction (p<0.002) in tumor growth accompanied by decreased tumor cell proliferation as evident from reduced tumor size and Ki67 staining. Accumulation of NCe was found in tumors isolated from treated group using transmission electron microscopy (TEM) and inductively coupled plasma mass spectroscopy (ICP-MS). Reduction of the tumor mass was accompanied by attenuation of angiogenesis, as observed by reduced CD31 staining and specific apoptosis of vascular endothelial cells. Collectively, these results indicate that cerium oxide based NCe is a novel nanoparticle that can potentially be used as an anti-angiogenic therapeutic agent in ovarian cancer.

SUBMITTER: Giri S

PROVIDER: S-EPMC3561344 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer.

Giri Shailendra S Karakoti Ajay A Graham Rondell P RP Maguire Jacie L JL Reilly Christopher M CM Seal Sudipta S Rattan Ramandeep R Shridhar Viji V

PloS one 20130131 1

Ovarian cancer (OvCa) is the fifth most common cause of death from all cancers among women in United Sates and the leading cause of death from gynecological malignancies. While most OvCa patients initially respond to surgical debulking and chemotherapy, 75% of patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with OvCa. In this context, we have developed and engineered Nanoceria (NCe), nanopartic ...[more]

PMID: 23382918

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Project description:BackgroundSchistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni.MethodsFifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF β1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed.ResultsA significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-β1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05).ConclusionOur results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Dataset Information

Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer.

Publications

Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer.

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