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...
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| Format: | Article |
| Language: | English |
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Serbian Chemical Society
2018-01-01
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| Series: | Journal of the Serbian Chemical Society |
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| Online Access: | http://www.doiserbia.nb.rs/img/doi/0352-5139/2018/0352-51391700108F.pdf |
| _version_ | 1819036267899256832 |
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| author | Fatima Ayesha Abdul Bustamam Ahmad H. Abdullah Rasedee Karjiban Roghayeh Abedi Lee Vannajan Sanghiran |
| author_facet | Fatima Ayesha Abdul Bustamam Ahmad H. Abdullah Rasedee Karjiban Roghayeh Abedi Lee Vannajan Sanghiran |
| author_sort | Fatima Ayesha |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T08:02:49Z |
| format | Article |
| id | doaj.art-ea87c168ca7c4c05984af83ae1a76dc1 |
| institution | Directory Open Access Journal |
| issn | 0352-5139 1820-7421 |
| language | English |
| last_indexed | 2024-12-21T08:02:49Z |
| publishDate | 2018-01-01 |
| publisher | Serbian Chemical Society |
| record_format | Article |
| series | Journal of the Serbian Chemical Society |
| spelling | doaj.art-ea87c168ca7c4c05984af83ae1a76dc12022-12-21T19:10:53ZengSerbian Chemical SocietyJournal of the Serbian Chemical Society0352-51391820-74212018-01-0183557559110.2298/JSC170313108F0352-51391700108FDocking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancerFatima Ayesha0Abdul Bustamam Ahmad H.1Abdullah Rasedee2Karjiban Roghayeh Abedi3Lee Vannajan Sanghiran4University Putra Malaysia, Institute of Biosciences, UPM-MAKNA Cancer Research Laboratory, Serdang, Malaysia + Quest International University Perak, Faculty of Pharmacy, Jalan Raja Permaisuri Bainun, Ipoh, Perak, MalaysiaUniversity Putra Malaysia, Institute of Biosciences, UPM-MAKNA Cancer Research Laboratory, Serdang, MalaysiaUniversity Putra Malaysia, Institute of Biosciences, UPM-MAKNA Cancer Research Laboratory, Serdang, Malaysia + University Putra Malaysia, Faculty of Veterinary Medicine, Department of Microbiology and Pathology, Serdang, MalaysiaUniversity Putra Malaysia, Faculty of Science, Department of Chemistry, Serdang, Malaysia + Universiti Putra Malaysia, Faculty of Biotechnology and Biomolecular Sciences, Enzyme and Microbial Technology Research Centre, Selangor, MalaysiaUniversity Malaya, Faculty of Science, Department of Chemistry, Petaling Jaya, Selangor, MalaysiaBreast 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.http://www.doiserbia.nb.rs/img/doi/0352-5139/2018/0352-51391700108F.pdfzerumboneWnt-β-catenin pathwayfrizzled (Fzd) proteinβ-catenin-transcription factor 4 complexmolecular docking |
| spellingShingle | Fatima Ayesha Abdul Bustamam Ahmad H. Abdullah Rasedee Karjiban Roghayeh Abedi Lee Vannajan Sanghiran Docking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancer Journal of the Serbian Chemical Society zerumbone Wnt-β-catenin pathway frizzled (Fzd) protein β-catenin-transcription factor 4 complex molecular docking |
| title | Docking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancer |
| title_full | Docking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancer |
| title_fullStr | Docking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancer |
| title_full_unstemmed | Docking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancer |
| title_short | Docking studies reveal zerumbone targets β-catenin of the Wnt-β-catenin pathway in breast cancer |
| title_sort | docking studies reveal zerumbone targets β catenin of the wnt β catenin pathway in breast cancer |
| topic | zerumbone Wnt-β-catenin pathway frizzled (Fzd) protein β-catenin-transcription factor 4 complex molecular docking |
| url | http://www.doiserbia.nb.rs/img/doi/0352-5139/2018/0352-51391700108F.pdf |
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