title: Fe-MIL-101 exhibits selective cytotoxicity and inhibition of angiogenesis in ovarian cancer cells via downregulation of MMP.
abstract: Though metal-organic frameworks (MOFs) have inspired potential applications in biomedicine, cytotoxicity studies of MOFs have been relatively rare. Here we demonstrate for the first time that an easily available MOF, Fe-MIL-101, possesses intrinsic activity against human SKOV3 ovarian cancer cells and suppress the proliferation of SKOV3 cells (IC50 = 23.6 μg mL(-1)) and normal mouse embryonic fibroblasts (BABL-3T3, IC50 = 78.3 μg mL(-1)) cells. It was more effective against SKOV3 cells than typical anticancer drugs such as artesunate (ART, IC50 = 96.9 μg mL(-1)) and oxaliplatin (OXA, IC50 = 64.4 μg mL(-1)), but had less effect on normal BABL-3T3 cells compared with ART (IC50 = 36.6 μg mL(-1)) and OXA (IC50 = 13.8 μg mL(-1)). Fe-MIL-101 induced apoptosis of human umbilical vein endothelial cells (HUVECs) via G0/G1 cell cycle arrest and decreased the mitochondrial membrane potential in HUVECs and induced apoptosis. Furthermore, Fe-MIL-101 exhibited stronger antiangiogenic effects in HUVEC cells than antiangiogenic inhibitor (SU5416) via downregulation the expression of MMP-2/9. Our results reveal a new role of Fe-MIL-101 as a novel, non-toxic anti-angiogenic agent that restricted ovarian tumour growth. These findings could open a new avenue of using MOFs as potential therapeutics in angiogenesis-dependent diseases, including ovarian cancer.
authors.affiliation: Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, The Universities' Center for Photocatalytic Treatment of Pollutants in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Energy, School of Chemical Sciences &Technology, Yunnan University, Kunming 650091, P.R. China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, The Universities' Center for Photocatalytic Treatment of Pollutants in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Energy, School of Chemical Sciences &Technology, Yunnan University, Kunming 650091, P.R. China.
authors.forename: Daomei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, The Universities' Center for Photocatalytic Treatment of Pollutants in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Energy, School of Chemical Sciences &Technology, Yunnan University, Kunming 650091, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, The Universities' Center for Photocatalytic Treatment of Pollutants in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Energy, School of Chemical Sciences &Technology, Yunnan University, Kunming 650091, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: He
authors.affiliation: Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, The Universities' Center for Photocatalytic Treatment of Pollutants in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Energy, School of Chemical Sciences &Technology, Yunnan University, Kunming 650091, P.R. China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Duan
authors.affiliation: Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, The Universities' Center for Photocatalytic Treatment of Pollutants in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Energy, School of Chemical Sciences &Technology, Yunnan University, Kunming 650091, P.R. China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Shao
authors.affiliation: Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, The Universities' Center for Photocatalytic Treatment of Pollutants in Yunnan Province, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Energy, School of Chemical Sciences &Technology, Yunnan University, Kunming 650091, P.R. China.
authors.forename: Minfang
authors.initials: M
authors.lastname: Nie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D056831:Coordination Complexes / Q000378:metabolism*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007501:Iron / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism*; D000073396:Metal-Organic Frameworks; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; C000589635:MIL-101; D061965:Matrix Metalloproteinase Inhibitors; D000073396:Metal-Organic Frameworks; D007501:Iron