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–β-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–β-catenin pathway is relatively unknown, e...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Serbian Chemical Society
2018-01-01
|
Series: | Journal of the Serbian Chemical Society |
Subjects: | |
Online Access: | http://www.doiserbia.nb.rs/img/doi/0352-5139/2018/0352-51391700108F.pdf |
Summary: | Breast cancer is the second most common cancer among women worldwide. The Wnt–β-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–β-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–β-catenin pathway were evaluated in this study. The results suggest that zerumbone has a strong affinity for free β-catenin in the cytoplasm, as well as the β-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 α,β-unsaturated carbonyl facilitated its interaction with positively charged residues, such as Lys345, Arg386 and Asn415 in the β-catenin binding pocket. However, the Wnt protein and its frizzled receptor showed no attraction to zerumbone. |
---|---|
ISSN: | 0352-5139 1820-7421 |