Discovery of oxyepiberberine as a novel tubulin polymerization inhibitor and an anti-colon cancer agent against LS-1034
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PRECLINICAL STUDIES
Discovery of oxyepiberberine as a novel tubulin polymerization inhibitor and an anti-colon cancer agent against LS-1034 cells Hanbing Ning 1 & Wenquan Lu 1 & Qiaoyu Jia 1 & Jingyun Wang 1 & Tingting Yao 1 & Shuai Lv 1 & Yingxia Li 1 & Hongtao Wen 1 Received: 1 July 2020 / Accepted: 16 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study aimed to investigate the anti-cancer effects and underlying mechanisms of oxyepiberberine on LS-1034 human colon cancer cells. The anti-proliferative effects of six derivatives of oxyepiberberine on colon cancer cells were assessed. Among six derivatives, oxyepiberberine showed the greatest antiproliferative effect on LS-1034 cells with an IC50 value of 1.36 μM. Oxyepiberberine also induced apoptosis and inhibited migration of LS-1034 cells in a concentration-dependent manner. Importantly, oxyepiberberine was identified as a potent tubulin polymerization inhibitor. The tubulin polymerization inhibitory effects of oxyepiberberine in a concentration-dependent manner with an IC50 value of 1.26 μM were observed. A xenograft mouse model of colon cancer showed that oxyepiberberine could suppress tumor growth without an obvious toxicity. Conclusion Oxyepiberberine was found as a novel tubulin polymerization inhibitor, and it could be a promising agent to treat colon cancer. Keywords Oxyepiberberine . LS-1034 cells . Apoptosis . Tubulin polymerization . Colon cancer xenograft
Introduction Coptis chinensis Franch. (Huanglian), an important medicinal plant in the Ranunculaceae. C. chinensis, has been extensively used in traditional Chinese medicine [1]. It was reported that Coptis chinensis Franch rhizome has various pharmacological properties, such as anti-oxidant, anti-cancer, and anti-inflammatory activities [2–5]. Recently, more than 40 alkaloid derivatives have been isolated from Coptis chinensis Franch. Oxyepiberberine, as an alkaloid from Coptis chinensis Franch., can be used to treat gastrointestinal diseases [6]. However, anti-tumor effects and molecular target of oxyepiberberine have still remained elusive.
* Hanbing Ning [email protected] 1
Department of Digestive Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
The exploration of tumor physiology has exposed a lot of molecular targets for the selective therapeutic intervention by antitumor drugs [7]. Microtubules as basic cell components are not only involved in maintaining cell morphology, but also a variety of cellular processes including signaling pathways, intracellular macromolecular assembly and cell division [8]. Hence, exploration of their chemical molecules which target tubulin to hamper the dynamics of tubu
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