Downregulation of Tumor Growth and Invasion by Redox-Active Nanoparticles

被引:151
作者
Alili, Lirija [1 ]
Sack, Maren [1 ]
von Montfort, Claudia [1 ,2 ]
Giri, Shailendra [3 ]
Das, Soumen [4 ]
Carroll, Kate S. [5 ]
Zanger, Klaus [6 ]
Seal, Sudipta [4 ]
Brenneisen, Peter [1 ]
机构
[1] Univ Dusseldorf, Inst Biochem & Mol Biol 1, Fac Med, D-40225 Dusseldorf, Germany
[2] IIBB CSIC, Dept Cell Death & Proliferat, Barcelona, Spain
[3] Mayo Clin, Coll Med, Dept Expt Pathol, Rochester, MN USA
[4] Univ Cent Florida, Nanosci & Technol Ctr NSTC, Adv Mat Proc & Anal Ctr, Orlando, FL 32816 USA
[5] Scripps Res Inst, Dept Chem, Jupiter, FL USA
[6] Univ Dusseldorf, Fac Med, Inst Anat 2, Dusseldorf, Germany
基金
美国国家科学基金会;
关键词
NADPH OXIDASE; CERIUM OXIDE; IN-VIVO; CELLS; APOPTOSIS; MELANOMA; FIBROBLASTS; ANTIOXIDANT; ACTIVATION; PH;
D O I
10.1089/ars.2012.4831
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aims: Melanoma is the most aggressive type of malignant skin cancer derived from uncontrolled proliferation of melanocytes. Melanoma cells possess a high potential to metastasize, and the prognosis for advanced melanoma is rather poor due to its strong resistance to conventional chemotherapeutics. Nanomaterials are at the cutting edge of the rapidly developing area of nanomedicine. The potential of nanoparticles for use as carrier in cancer drug delivery is infinite with novel applications constantly being tested. The noncarrier use of cerium oxide nanoparticles (CNPs) is a novel and promising approach, as those particles per se show an anticancer activity via their oxygen vacancy-mediated chemical reactivity. Results: In this study, the question was addressed of whether the use of CNPs might be a valuable tool to counteract the invasive capacity and metastasis of melanoma cells in the future. Therefore, the effect of those nanoparticles on human melanoma cells was investigated in vitro and in vivo. Concentrations of polymer-coated CNPs being nontoxic for stromal cells showed a cytotoxic, proapoptotic, and anti-invasive capacity on melanoma cells. In vivo xenograft studies with immunodeficient nude mice showed a decrease of tumor weight and volume after treatment with CNPs. Innovation: In summary, the redox-active CNPs have selective pro-oxidative and antioxidative properties, and this study is the first to show that CNPs prevent tumor growth in vivo. Conclusion: The application of redox-active CNPs may form the basis of new paradigms in the treatment and prevention of cancers.
引用
收藏
页码:765 / 778
页数:14
相关论文
共 66 条
[1]   HMEC-1 - ESTABLISHMENT OF AN IMMORTALIZED HUMAN MICROVASCULAR ENDOTHELIAL-CELL LINE [J].
ADES, EW ;
CANDAL, FJ ;
SWERLICK, RA ;
GEORGE, VG ;
SUMMERS, S ;
BOSSE, DC ;
LAWLEY, TJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (06) :683-690
[2]  
Alili L, 2009, CANC RES S, V69, pC42
[3]   Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor-stroma interactions [J].
Alili, Lirija ;
Sack, Maren ;
Karakoti, Ajay S. ;
Teuber, Sarah ;
Puschmann, Katharina ;
Hirst, Suzanne M. ;
Reilly, Christopher M. ;
Zanger, Klaus ;
Stahl, Wilhelm ;
Das, Soumen ;
Seal, Sudipta ;
Brenneisen, Peter .
BIOMATERIALS, 2011, 32 (11) :2918-2929
[4]  
[Anonymous], 2010, CANCER
[5]   Negative and positive regulation of HIF-1:: A complex network [J].
Bárdos, JI ;
Ashcroft, M .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2005, 1755 (02) :107-120
[6]   TERMINAL DIFFERENTIATION, AGING, APOPTOSIS, AND SPONTANEOUS TRANSFORMATION IN FIBROBLAST STEM-CELL SYSTEMS INVIVO AND INVITRO [J].
BAYREUTHER, K ;
FRANCZ, PI ;
GOGOL, J ;
KONTERMANN, K .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES, 1992, 663 :167-179
[7]  
Bhatia S, 2009, ONCOLOGY-NY, V23, P488
[8]   Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis - Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells [J].
Boulares, AH ;
Yakovlev, AG ;
Ivanova, V ;
Stoica, BA ;
Wang, GP ;
Iyer, S ;
Smulson, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (33) :22932-22940
[9]   Central role of ferrous/ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP)-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts [J].
Brenneisen, P ;
Wenk, J ;
Klotz, LO ;
Wlaschek, M ;
Briviba, K ;
Krieg, T ;
Sies, H ;
Scharffetter-Kochanek, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (09) :5279-5287
[10]   Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species [J].
Cat, Bahar ;
Stuhlmann, Dominik ;
Steinbrenner, Holger ;
Alili, Lirija ;
Holtkoetter, Olaf ;
Sies, Helmut ;
Brenneisen, Peter .
JOURNAL OF CELL SCIENCE, 2006, 119 (13) :2727-2738