Docking studies reveal zerumbone targets β-catenin of the Wnt–β-catenin pathway in breast cancer

Ayesha Fatima, Ahmad Bustamam H. Abdul, Rasedee Abdullah, Roghayeh Abedi Karjiban, Vannajan Sanghiran Lee

Abstract


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.


Keywords


zerumbone; Wnt–β-catenin pathway; frizzled (Fzd) protein; β-cat¬enin–transcription factor 4 complex; molecular docking

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DOI: https://doi.org/10.2298/JSC170313108F

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