Glochidiol, a natural triterpenoid, exerts its anti-cancer effects by targeting the colchicine binding site of tubulin
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Glochidiol, a natural triterpenoid, exerts its anti-cancer effects by targeting the colchicine binding site of tubulin Hongjie Chen 1 & Lijun Miao 1 & Fengxiang Huang 1 & Yali Yu 1 & Qiang Peng 1 & Ying Liu 1 & Xixi Li 1 & Hong Liu 1 Received: 25 July 2020 / Accepted: 21 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Glochidiol has been shown to have potentially antiproliferative activity in vitro, however its anticancer mechanisms specifically against lung cancer remain unknown. This study aimed to investigate the anti-lung cancer effects of glochidiol in HCC-44 cells in vitro and in vivo. In the present study, glochidiol was found to have potent antiproliferative activity against lung cancer cell lines NCI-H2087, HOP-62, NCI-H520, HCC-44, HARA, EPLC-272H, NCI-H3122, COR-L105 and Calu-6 with IC50 values of 4.12 µM, 2.01 µM, 7.53 µM, 1.62 µM, 4.79 µM, 7.69 µM, 2.36 µM, 6.07 µM and 2.10 µM, respectively. In vivo, glochidiol was found to effectively inhibit lung cancer HCC-44 xenograft tumor growth in nude mice. Docking analysis found that glochidiol forms hydrogen bonds with residues of tubulin. Glochidiol was also found to inhibit tubulin polymerization in vitro with an IC50 value of 2.76 µM. Immunofluorescence staining and EBI competition assay suggest that glochidiol may interact with tubulin by targeting the colchicine binding site. Thus, glochidiol might be a novel colchicine binding site inhibitor with the potential to treat lung cancer. Keywords Glochidiol . Lung cancer . Colchicine binding site . HCC-44 Xenograft tumor
Introduction Lung cancer is one of the most common malignant tumors in the world with significant morbidity and mortality [1–3]. It is broadly categorized as either small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) [4]. Although there have been advances in lung cancer therapeutics in recent years, effective drugs to treat lung cancer are still lacking and there is an urgent need for new anti-lung cancer drugs [5, 6]. Many chemotherapeutic drugs have been isolated from medicinal plants with these natural products exhibiting potent
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10637-020-01013-1) contains supplementary material, which is available to authorized users. * Hong Liu [email protected] 1
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
anticancer activity in vitro and in vivo [7–9]. Clinical research has shown that natural products are widely used in the treatment of lung cancer [10, 11]. Glochidiol, as a natural triterpenoid, has been found to exhibit inhibitory effects against MCF-7 and SF-268 cells in vitro [12]. It has also shown a strong inhibitory effect on mouse skin tumor promotion by inducing apoptosis [13]. However, anticancer mechanisms of glochidiol and its effects against lung cancer remain unknown. Microtubules play important roles in various cellular pro
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