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
  • 1. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 2. Integrated Care Management Center, West China Hospital, Sichuan University, China. Electronic address: [email protected].
  • 3. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 4. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 5. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 6. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 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: [email protected].
  • 8. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
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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