A novel co-drug of aspirin and ursolic acid interrupts adhesion, invasion and migration of cancer cells to vascular endothelium via regulating EMT and EGFR-mediated signaling pathways: multiple targets for cancer metastasis prevention and treatment

Jemal, 2015, Cancer statistics, 2015, CA Cancer J Clin, 65, 5, 10.3322/caac.21254

Fedewa, 2012, Cancer treatment and survivorship statistics, 2012, CA Cancer J Clin, 62, 220, 10.3322/caac.21149

Perret, 2010, Pharmacological strategies and micrometastasis: what is known?, What must be done? Minerva Med, 101, 163

Li, 2015, EMT, CTCs and CSCs in tumor relapse and drug-resistance, Oncotarget, 6, 10697, 10.18632/oncotarget.4037

Christofori, 2015, The relevance of EMT in breast cancer metastasis: Correlation or causality?, FEBS Lett, 589, 1577, 10.1016/j.febslet.2015.05.002

Kawakami, 2009, Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells, Cancer cell, 15, 195, 10.1016/j.ccr.2009.01.023

Li, 2015, The roles of signaling pathways in epithelial-to-mesenchymal transition of PVR, Mol Vis, 21, 706

Papageorgis, 2015, TGFbeta Signaling in Tumor Initiation, Epithelial-to-Mesenchymal Transition, and Metastasis, J Oncol, 2015, 587193, 10.1155/2015/587193

Zupancic, 2001, Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance of ursolic acid, J Ethnopharmacol, 75, 125, 10.1016/S0378-8741(00)00396-2

Sharma, 2016, Ursolic acid (UA): A metabolite with promising therapeutic potential, Life Sci, 146, 201, 10.1016/j.lfs.2016.01.017

Guo, 2011, andanticancer activity evaluation of ursolic acid derivatives, Eur J Med Chem, 46, 2652, 10.1016/j.ejmech.2011.03.050

Bishayee, 2013, Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies, Biochem Pharmacol, 85, 1579, 10.1016/j.bcp.2013.03.006

Adams, 2012, Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease, PloS one, 7, e39332, 10.1371/journal.pone.0039332

Shao, 2015, Synthesis and Biological Evaluation of Novel Ursolic acid Derivatives as Potential Anticancer Prodrugs, Chem Biol Drug Des, 86, 1397, 10.1111/cbdd.12608

Bishayee, 2013, Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem, Pharmacol, 85, 1579

Sunil, 2012, Ursolic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in an Orthotopic Nude Mouse Model by Targeting Multiple Cell Signaling Pathways: Chemosensitization with Capecitabine, Clin Cancer Res, 18, 4942, 10.1158/1078-0432.CCR-11-2805

Masterova, 2006, Antiprotease and antimetastatic activity of ursolic acid isolated from Salvia officinalis, Z Naturforsch C, 61, 777, 10.1515/znc-2006-11-1203

Shao, 2015, A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis, Oncotarget, 6, 9295, 10.18632/oncotarget.3261

Zhu, 2015, A bioinformatic and mechanistic study elicits the antifibrotic effect of ursolic acid through the attenuation of oxidative stress with the involvement of ERK, PI3K/Akt, and p38 MAPK signaling pathways in human hepatic stellate cells and rat liver, Drug Des Devel Ther, 9, 3989, 10.2147/DDDT.S85426

Yin, 2011, Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines, Toxicol, 25, 1274

Sharma, 2016, Ursolic acid (UA): A metabolite with promising therapeutic potential, Life Sci, 146, 201, 10.1016/j.lfs.2016.01.017

Lohr, 2003, Spontaneous hemarthrosis of the knee associated with clopidogrel and aspirin treatment, Z Rheumatol, 62, 80, 10.1007/s00393-003-0420-3

Bhat, 2015, Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention, Tumour Biol, 37, 1727

Lanas, 2015, NSAIDS and gastrointestinal cancer, Prostaglandins Other Lipid Mediat, 120, 91, 10.1016/j.prostaglandins.2015.06.001

Liu, 2015, Chemopreventive effects of aspirin at a glance, Biophys Acta, 1855, 254

Farag, 2015, Can Aspirin and Cancer Prevention be Ageless Companions?, J Clin Diagn Res, 9, XE01

Banerjee, 2015, Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition, Lab Invest, 95, 702, 10.1038/labinvest.2015.49

Wang, 2016, Aspirin Inhibits LPS-Induced Expression of PI3K/Akt, ERK, NF-κB, CX3CL1, and MMPs in Human Bronchial Epithelial Cells, Inflammation, 39, 643, 10.1007/s10753-015-0289-8

Kim, 2014, Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer, Int J Cancer, 134, 519, 10.1002/ijc.28381

Xie, 2015, Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil, Oncotarget, 6, 35157, 10.18632/oncotarget.6038

Zanker, 1998, Integrins, cell matrix interactions and cell migration strategies: fundamental differences in leukocytes and tumor cells, Cell Adhes Commun, 6, 225, 10.3109/15419069809004478

Leung, 2015, Activin B induces human endometrial cancer cell adhesion, migration and invasion by up-regulating integrin beta3 via SMAD2/3 signaling, Oncotarget, 6, 31659, 10.18632/oncotarget.5229

Marszałek, 2015, Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities, Molecules, 20, 20614, 10.3390/molecules201119721

Moon, 2015, Natural Products for Chemoprevention of Breast Cancer, J Cancer Prev, 20, 223, 10.15430/JCP.2015.20.4.223

Lei, 2014, Review on anti-tumor effect of triterpene acid compounds, J Cancer Res Ther, 10, 14, 10.4103/0973-1482.139746

Liu, 2015, Chemopreventive effects of aspirin at a glance, Biochim Biophys Acta, 1855, 254

Rainger, 2014, Adhesion of tumor cells to matrices and endothelium, Methods Mol Biol, 1070, 57, 10.1007/978-1-4614-8244-4_5

Arabzadeh, 2013, Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis, Cancer Metastasis Rev, 32, 643, 10.1007/s10555-013-9444-6

Krishnan, 2012, Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine, Clin Cancer Res, 18, 4942, 10.1158/1078-0432.CCR-11-2805

Veeranjaneyulu, 2014, Enhancement of matrix metalloproteinase 2 and 9 inhibitory action of minocycline by aspirin: an approach to attenuate outcome of acute myocardial infarction in diabetes, Arch Med Res, 45, 203, 10.1016/j.arcmed.2014.01.008

Proctor, 2015, Nonsteroidal anti-inflammatory drugs for dysmenorrhoea, Cochrane Database Syst Rev, 7, CD001751

Kelly, 2014, Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term, Cochrane Database Syst Rev, 6, CD003101

CC, 2008, Acetylsalicylic acid regulates MMP-2 activity and inhibits colorectal invasion of murine B16F0 melanoma cells in C57BL/6J mice: effects of prostaglandin F(2)alpha, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 63, 522

Rafii, 2015, Epithelial to Mesenchymal Transition in a Clinical Perspective, J Oncol, 2015, 792182

Chaplain, 2008, Modeling the Influence of the E-Cadherin-β-Catenin Pathway in Cancer Cell Invasion: A Multiscale Approach, Biophysical Journal, 95, 155, 10.1529/biophysj.107.114678

Zheng, 2011, E-cadherin/β-catenin complex and the epithelial barrier, J Biomed Biotechnol, 2011, 567305

Wu, 2015, The role of CD44 in epithelial-mesenchymal transition and cancer development, Onco Targets Ther, 8, 3783, 10.2147/OTT.S95470

Schofer, 2010, CD44: survival and metastasis in chondrosarcoma, Osteoarthritis Cartilage, 18, 849, 10.1016/j.joca.2010.02.007

Kay, 2015, CD44 increases the efficiency of distant metastasis of breast cancer, Oncotarget, 6, 11465, 10.18632/oncotarget.3410

Nachtigal, 2007, BMP4 induces EMT and Rho GTPase activation in human ovarian cancer cells, Carcinogenesis, 28, 1153, 10.1093/carcin/bgm015

Blandizzi, 2015, Adverse reactions to oncologic drugs: spontaneous reporting and signal detection, Expert Rev Clin Pharmacol, 8, 61, 10.1586/17512433.2015.974555

Jia, 2014, Synergism of ursolic acid derivative US597 with 2-deoxy-D-glucose to preferentially induce tumor cell death by dual-targeting of apoptosis and glycolysis, Sci Rep, 4, 5006, 10.1038/srep05006

Jia, 2015, UP12, a novel ursolic acid derivative with potential for targeting multiple signaling pathways in hepatocellular carcinoma, Biochem Pharmacol, 93, 151, 10.1016/j.bcp.2014.11.014

Jia, 2014, Synthesis, spectral characterization, andcellular activities of metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486), AAPS J, 16, 289, 10.1208/s12248-013-9559-2

Wang, 2014, Nitric oxide inhibits hetero-adhesion of cancer cells to endothelial cells: restraining circulating tumor cells from initiating metastatic cascade, Sci Rep, 4, 4344, 10.1038/srep04344