Docking Studies Reveal Zerumbone Targets b-catenin of the Wnt-b-catenin Pathway in Breast Cancer

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

Abstract


Breast cancer is the second most common cancer among women world-wide. The Wnt-b-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zerumbet Roscoe, on the Wnt-b-catenin pathway is relatively unknown especially detailed molecular studies are yet unpublished. Using Chemistry at HARvard Macromolecular Mechanics (CHARMm) forcefield based docking protocol, CDOCKER, this study evaluated the molecular interactions between zerumbone and the key proteins of the Wnt-b-catenin pathway. Our results suggest that zerumbone has a strong affinity for free b-catenin in the cytoplasm as well as the b-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,b-unsaturated hydrocarbon facilitates its interaction with positively charged residues like Lys345, Arg386 and Asn 415 in the b-catenin binding pocket. However, the Wnt protein and its frizzled receptor showed no attraction to zerumbone. 


Keywords


zerumbone; Wnt-beta catenin pathway; frizzled (Fzd) protein; -catenin-transcription factor 4 complex; molecular docking

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DOI: http://dx.doi.org/10.2298/JSC170313108F

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