A Novel Galectin-1 Inhibitor Discovered Through One-Bead Two-Compound Library Potentiates the Antitumor Effects of Paclitaxel

Overview

Journal Mol Cancer Ther

Date 2017 Apr 12

PMID 28396365

Citations 18

Authors

Tsung-Chieh Shih

Ruiwu Liu

Gabriel Fung

Gaurav Bhardwaj

Paramita M Ghosh

Kit S Lam

Affiliations

Soon will be listed here.

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) Furthermore, 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. .

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