2. Academic Validation
  3. The cytotoxic natural compound erianin binds to colchicine site of β-tubulin and overcomes taxane resistance

The cytotoxic natural compound erianin binds to colchicine site of β-tubulin and overcomes taxane resistance

  • Bioorg Chem. 2024 Jun 17:150:107569. doi: 10.1016/j.bioorg.2024.107569.
Wei Yan 1,  Yongzhao Zhou 2,  Xue Yuan 3,  Peng Bai 4,  Minghai Tang 5,  Lijuan Chen 6,  Haoche Wei 7,  Jianhong Yang 8
Affiliations

Affiliations

  • 1 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: yanxiaowei369@sina.com.
  • 2 Integrated Care Management Center, West China Hospital, Sichuan University, China. Electronic address: yongzhaozhou001@wchscu.cn.
  • 3 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: yuanxue69@163.com.
  • 4 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: bp1493@163.com.
  • 5 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: tangminghai1982@126.com.
  • 6 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: 15882412979@163.com.
  • 7 Department of General Surgery, Gastric Cancer Center, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. Electronic address: maria2588@sina.cn.
  • 8 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: yjh1988@scu.edu.cn.
PMID: 38905886 DOI: 10.1016/j.bioorg.2024.107569
Abstract

Erianin, a natural compound derived from Dendrobium, has shown significant Anticancer properties against a wide range of Cancer cells. Despite the identification of multiple mechanisms of action for erianin, none of these mechanisms fully account for its broad-spectrum effect. In this study, we aimed to identify the cellular target and underlying mechanism responsible for the broad-spectrum antitumor effects of erianin. We found that erianin effectively inhibited tubulin polymerization in Cancer cells and purified tubulin. Through competition binding assays and X-ray crystallography, it was revealed that erianin bound to the colchicine site of β-tubulin. Importantly, the X-ray crystal structure of the tubulin-erianin complex was solved, providing clear insight into the orientation and position of erianin in the colchicine-binding site. Erianin showed activity against paclitaxel-resistant cells, evidenced by G2/M cell cycle arrest, apoptosis-related PARP and Caspase-3 cleavage, and in vivo xenograft studies. The study concluded that erianin bound reversibly to the colchicine site of β-tubulin, inhibited tubulin polymerization, and displayed Anticancer activity against paclitaxel-resistant cells, offering valuable insights for further exploration as potential Anticancer agents.

Keywords

Colchicine site; Erianin; Microtubule; Paclitaxel resistant; Tubulin.

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