Chemical proteomics reveal CD147 as a functional target of pseudolaric acid B in human cancer cells.

CD147 is a glycosylated transmembrane protein highly expressed on the surface of various tumor cells which plays vital roles in tumor invasion, progression and metastasis. We report the discovery of the natural product pseudolaric acid B (PAB) directly targeting CD147 by chemical proteomics utilizing a PAB-derived photoaffinity probe which could serve as a novel type of anticancer reagent.

[1]  Carl W. Miller,et al.  Cyr61, a Member of CCN Family, Is a Tumor Suppressor in Non-Small Cell Lung Cancer* , 2001, The Journal of Biological Chemistry.

[2]  S. Sze,et al.  Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. , 2013, Angewandte Chemie.

[3]  Youli Xiao,et al.  Global profiling of cellular targets of gambogic acid by quantitative chemical proteomics. , 2016, Chemical communications.

[4]  L. Lau,et al.  The Angiogenic Factor Cyr61 Activates a Genetic Program for Wound Healing in Human Skin Fibroblasts* , 2001, The Journal of Biological Chemistry.

[5]  Jian Ding,et al.  Pseudolarix Acid B, a New Tubulin-Binding Agent, Inhibits Angiogenesis by Interacting with a Novel Binding Site on Tubulin , 2006, Molecular Pharmacology.

[6]  Karunakaran A Kalesh,et al.  Target identification of natural and traditional medicines with quantitative chemical proteomics approaches. , 2016, Pharmacology & therapeutics.

[7]  Ning Wen,et al.  Crystal Structure of HAb18G/CD147 , 2008, Journal of Biological Chemistry.

[8]  Dan Sun,et al.  Pseudolaric acid B inhibits gastric cancer cell metastasis in vitro and in haematogenous dissemination model through PI3K/AKT, ERK1/2 and mitochondria‐mediated apoptosis pathways , 2017, Experimental Cell Research.

[9]  P. Zhu,et al.  A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells , 2016, Oncotarget.

[10]  S. Sieber,et al.  Target identification of natural products by activity based protein profiling and a whole proteome inventory of background photocrosslinker binding , 2016 .

[11]  G. Ma,et al.  Selective inhibition of human leukemia cell growth and induction of cell cycle arrest and apoptosis by pseudolaric acid B , 2010, Journal of Cancer Research and Clinical Oncology.

[12]  Liang Liu,et al.  Pseudolaric acid B suppresses T lymphocyte activation through inhibition of NF‐κB signaling pathway and p38 phosphorylation , 2009, Journal of cellular biochemistry.

[13]  B. Xiong,et al.  Studies on anti-tumour activities of pseudolaric acid-B (PLAB) and its mechanism of action , 2006, Journal of Asian natural products research.

[14]  M. Wright,et al.  Chemical proteomics approaches for identifying the cellular targets of natural products , 2016, Natural product reports.

[15]  T. Ikejima,et al.  Protein tyrosine kinase, JNK, and ERK involvement in pseudolaric acid B-induced apoptosis of human breast cancer MCF-7 cells , 2008, Acta Pharmacologica Sinica.

[16]  B. Ko,et al.  Pseudolaric acids: isolation, bioactivity and synthetic studies. , 2010, Natural product reports.

[17]  Jongmin Park,et al.  Investigation of Specific Binding Proteins to Photoaffinity Linkers for Efficient Deconvolution of Target Protein. , 2016, ACS chemical biology.

[18]  E. Rosenthal,et al.  Anti-EMMPRIN Monoclonal Antibody as a Novel Agent for Therapy of Head and Neck Cancer , 2009, Clinical Cancer Research.

[19]  A. Minassi,et al.  An NMR spectroscopic method to identify and classify thiol-trapping agents: revival of Michael acceptors for drug discovery? , 2011, Angewandte Chemie.

[20]  G. Cordell,et al.  Pseudolaric acid B: NMR assignments, conformational analysis and cytotoxicity , 1989 .

[21]  Hannes Stockinger,et al.  Cancer-related issues of CD147. , 2010, Cancer genomics & proteomics.

[22]  B. Toole.  Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function. , 2003, Current topics in developmental biology.

[23]  J. Miao,et al.  CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells. , 2015, Molecular immunology.

[24]  H. Osada,et al.  Affinity-based target identification for bioactive small molecules , 2014 .

[25]  A. Qian,et al.  siRNA targeted against HAb18G/CD147 inhibits MMP-2 secretion, actin and FAK expression in hepatocellular carcinoma cell line via ERK1/2 pathway. , 2007, Cancer letters.

[26]  S. Qiu,et al.  Interaction of pseudolaric acid B with the colchicine site of tubulin. , 2012, Biochemical pharmacology.

[27]  Z. Miao,et al.  Pseudolaric Acid B Inhibits Angiogenesis and Reduces Hypoxia-Inducible Factor 1α by Promoting Proteasome-Mediated Degradation , 2004, Clinical Cancer Research.

[28]  L. Chow,et al.  Pseudolaric Acid B, a Novel Microtubule-Destabilizing Agent That Circumvents Multidrug Resistance Phenotype and Exhibits Antitumor Activity In vivo , 2005, Clinical Cancer Research.

[29]  H. Iwasaki,et al.  Emmprin (basigin/CD147): Matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression , 2006, Pathology international.