Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor
Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of soft tissue neoplasm with extremely poor prognosis and no effective medical options currently available. MPNSTs can occur either sporadically or in association with the neurofibromatosis type 1 (NF1) syndrome. Impor...
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Wiley
2018-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1732 |
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| author | Xiao‐Xiao Li Shi‐Jie Zhang Amy P. Chiu Lilian H. Lo Jian Huang Dewi K. Rowlands Jinhui Wang Vincent W. Keng |
| author_facet | Xiao‐Xiao Li Shi‐Jie Zhang Amy P. Chiu Lilian H. Lo Jian Huang Dewi K. Rowlands Jinhui Wang Vincent W. Keng |
| author_sort | Xiao‐Xiao Li |
| collection | DOAJ |
| description | Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of soft tissue neoplasm with extremely poor prognosis and no effective medical options currently available. MPNSTs can occur either sporadically or in association with the neurofibromatosis type 1 (NF1) syndrome. Importantly, activation of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, and WNT/CTNNB1 signaling pathways has been reported in both NF1‐related and late‐stage sporadic MPNSTs. In this study, we found that DAW22, a natural sesquiterpene coumarin compound isolated from Ferula ferulaeoides (Steud.) Korov., could inhibit cell proliferation and colony formation in five established human MPNST cancer cell lines. Further molecular mechanism exploration indicated that DAW22 could target the main components in the MPNST tumorigenic pathways: namely suppress phosphorylation of AKT and ERK, and reduce levels of non‐phospho (active) CTNNB1. Using the xenograft mouse model transplanted with human MPNST cancer cell line, daily treatment with DAW22 for 25 days was effective in reducing tumor growth. These results support DAW22 as an alternative therapeutic compound for MPNST treatment by affecting multiple signaling transduction pathways in its disease progression. |
| format | Article |
| id | doaj-art-0db10cd2d8874526bbe8274b43af2f43 |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2018-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-0db10cd2d8874526bbe8274b43af2f432025-08-20T03:04:30ZengWileyCancer Medicine2045-76342018-09-01794791480010.1002/cam4.1732Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumorXiao‐Xiao Li0Shi‐Jie Zhang1Amy P. Chiu2Lilian H. Lo3Jian Huang4Dewi K. Rowlands5Jinhui Wang6Vincent W. Keng7Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Kowloon Hong KongInstitute of Clinical Pharmacology Guangzhou University of Chinese Medicine Guangzhou ChinaDepartment of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Kowloon Hong KongDepartment of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Kowloon Hong KongDepartment of Medicinal Chemistry and Natural Medicine Chemistry (State‐Province Key Laboratories of Biomedicine‐Pharmaceutics of China) Harbin Medical University Harbin ChinaLaboratory Animal Services Centre The Chinese University of Hong Kong Sha Tin New Territories Hong KongDepartment of Medicinal Chemistry and Natural Medicine Chemistry (State‐Province Key Laboratories of Biomedicine‐Pharmaceutics of China) Harbin Medical University Harbin ChinaDepartment of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Kowloon Hong KongAbstract Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of soft tissue neoplasm with extremely poor prognosis and no effective medical options currently available. MPNSTs can occur either sporadically or in association with the neurofibromatosis type 1 (NF1) syndrome. Importantly, activation of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, and WNT/CTNNB1 signaling pathways has been reported in both NF1‐related and late‐stage sporadic MPNSTs. In this study, we found that DAW22, a natural sesquiterpene coumarin compound isolated from Ferula ferulaeoides (Steud.) Korov., could inhibit cell proliferation and colony formation in five established human MPNST cancer cell lines. Further molecular mechanism exploration indicated that DAW22 could target the main components in the MPNST tumorigenic pathways: namely suppress phosphorylation of AKT and ERK, and reduce levels of non‐phospho (active) CTNNB1. Using the xenograft mouse model transplanted with human MPNST cancer cell line, daily treatment with DAW22 for 25 days was effective in reducing tumor growth. These results support DAW22 as an alternative therapeutic compound for MPNST treatment by affecting multiple signaling transduction pathways in its disease progression.https://doi.org/10.1002/cam4.1732AKTapoptosisDAW22ERKMPNST |
| spellingShingle | Xiao‐Xiao Li Shi‐Jie Zhang Amy P. Chiu Lilian H. Lo Jian Huang Dewi K. Rowlands Jinhui Wang Vincent W. Keng Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor Cancer Medicine AKT apoptosis DAW22 ERK MPNST |
| title | Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor |
| title_full | Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor |
| title_fullStr | Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor |
| title_full_unstemmed | Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor |
| title_short | Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor |
| title_sort | targeting of akt erk ctnnb1 by daw22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor |
| topic | AKT apoptosis DAW22 ERK MPNST |
| url | https://doi.org/10.1002/cam4.1732 |
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