title: A Novel Galectin-1 Inhibitor Discovered through One-Bead Two-Compound Library Potentiates the Antitumor Effects of Paclitaxelin vivo.
abstract: Through the one-bead two-compound (OB2C) ultra-high-throughput screening method, we discovered a new small-molecule compound LLS2 that can kill a variety of cancer cells. Pull-down assay and LC/MS-MS indicated that galectin-1 is the target protein of LLS2. Galectin-1 is known to be involved in the regulation of proliferation, apoptosis, cell cycle, and angiogenesis. Binding of LLS2 to galectin-1 decreased membrane-associated H-Ras and K-Ras and contributed to the suppression of pErk pathway. Importantly, combination of LLS2 with paclitaxel (a very important clinical chemotherapeutic agent) was found to exhibit synergistic activity against several human cancer cell lines (ovarian cancer, pancreatic cancer, and breast cancer cells)in vitroFurthermore,in vivotherapeutic study indicated that combination treatment with paclitaxel and LLS2 significantly inhibits the growth of ovarian cancer xenografts in athymic mice. Our results presented here indicate that the OB2C combinatorial technology is a highly efficient drug screening platform, and LLS2 discovered through this method can be further optimized for anticancer drug development.Mol Cancer Ther; 16(7); 1212-23. ©2017 AACR.
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, California.
authors.forename: Tsung-Chieh
authors.initials: TC
authors.lastname: Shih
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, California. kslam@ucdavis.edu rwliu@ucdavis.edu.
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, California.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fung
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhardwaj
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, California.|Department of Urology, University of California Davis, Sacramento, California.|VA Northern California Health Care System, Sacramento, California.
authors.forename: Paramita M
authors.initials: PM
authors.lastname: Ghosh
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, California. kslam@ucdavis.edu rwliu@ucdavis.edu.
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D054852:Small Molecule Libraries / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D037483:Galectin 1; D054852:Small Molecule Libraries; D017239:Paclitaxel