Fe-MIL-101 exhibits selective cytotoxicity and inhibition of angiogenesis in ovarian cancer cells via downregulation of MMP

• Published in: Scientific reports Vol. 6; no. 1; p. 26126
• Main Authors: Wang, Jiaqiang, Chen, Daomei, Li, Bin, He, Jiao, Duan, Deliang, Shao, Dandan, Nie, Minfang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.05.2016; Nature Publishing Group
• Subjects: 13/2; 13/31; 631/67/1059/602; 631/80/84/750; Angiogenesis; Animals; Antineoplastic Agents - metabolism; Antineoplastic drugs; Antitumor agents; Apoptosis; Artesunate; Cell cycle; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Coordination Complexes - metabolism; Cytotoxicity; Embryo fibroblasts; Embryos; Endothelial cells; Female; Gelatinase A; Humanities and Social Sciences; Humans; Inhibitory Concentration 50; Iron - metabolism; Matrix Metalloproteinase Inhibitors - metabolism; Membrane potential; Metal-Organic Frameworks; Mice; Mitochondria; multidisciplinary; Neovascularization, Physiologic - drug effects; Ovarian cancer; Oxaliplatin; Science; Science (multidisciplinary); Tumors; Umbilical vein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep26126

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 (IC 50  = 23.6 μg mL −1 ) and normal mouse embryonic fibroblasts (BABL-3T3, IC 50  = 78.3 μg mL −1 ) cells. It was more effective against SKOV3 cells than typical anticancer drugs such as artesunate (ART, IC 50  = 96.9 μg mL −1 ) and oxaliplatin (OXA, IC 50  = 64.4 μg mL −1 ), but had less effect on normal BABL-3T3 cells compared with ART (IC 50  = 36.6 μg mL −1 ) and OXA (IC 50  = 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.