title: 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.
authors: Department of Experimental Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors: Shailendra
authors: S
authors: Giri
authors: Ajay
authors: A
authors: Karakoti
authors: Rondell P
authors: RP
authors: Graham
authors: Jacie L
authors: JL
authors: Maguire
authors: Christopher M
authors: CM
authors: Reilly
authors: Sudipta
authors: S
authors: Seal
authors: Ramandeep
authors: R
authors: Rattan
authors: Viji
authors: V
authors: Shridhar
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002563:Cerium / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use / Q000648:ultrastructure; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D047368:Tumor Burden / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D017382:Reactive Oxygen Species; D042442:Vascular Endothelial Growth Factors; D002563:Cerium; C030583:ceric oxide
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