Docking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancer
Breast cancer is the second most common cancer among women worldwide.The Wnt-ß-catenin pathway appears to be deregulated in most cancer cells including breast cancer.The role of zerumbone, the active sesquiterpene from Zingiber zerumbet Roscoe, on the Wnt-ß-catenin pathway is relatively unknown, esp...
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| Main Authors: | , , , , |
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| Format: | Article |
| Published: |
Serbian Chemical Society
2018
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| Subjects: | |
| Online Access: | http://eprints.um.edu.my/22086/ https://doi.org/10.2298/JSC170313108F |
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| Summary: | Breast cancer is the second most common cancer among women worldwide.The Wnt-ß-catenin pathway appears to be deregulated in most cancer cells including breast cancer.The role of zerumbone, the active sesquiterpene from Zingiber zerumbet Roscoe, on the Wnt-ß-catenin pathway is relatively unknown, especially detailed molecular studies have yet to be published. Using the Chemistry at HARvard Macromolecular Mechanics (CHARMm) force field-based docking protocol, CDOCKER, the molecular interactions between zerumbone and key proteins of the Wnt-ß-catenin pathway were evaluated in this study.The results suggest that zerumbone has a strong affinity for free ß-catenin in the cytoplasm, as well as the ß-catenin-transcription factor 4 complex in the nucleus.The overall hydrophobic nature of zerumbone allowed its interaction with other hydrophobic residues, such as Trp383, while its active a,ß-unsaturated carbonyl facilitated its interaction with positively charged residues, such as Lys345, Arg386 and Asn415 in the ß-catenin binding pocket. However, the Wnt protein and its frizzled receptor showed no attraction to zerumbone. |
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