A novel galectin-1 inhibitor discovered through one-bead two-compound library potentiates the antitumor effects of paclitaxel in vivo

Tsung Chieh Shih, Ruiwu Liu, Gabriel Fung, Gaurav Bhardwaj, Paramita M Ghosh, Kit Lam

Research output: Contribution to journalArticle

12 Scopus citations

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 vitro. Furthermore, in vivo therapeutic 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.

Original languageEnglish (US)
Pages (from-to)1212-1223
Number of pages12
JournalMolecular Cancer Therapeutics
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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