Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/80003
Title: Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor
Authors: Li XX 
Zhang, SJ
Chiu AP 
Lo LH 
Huang, J
Rowlands, DK
Wang, J
Keng, VW 
Keywords: AKT
Apoptosis
DAW22
ERK
MPNST
Issue Date: 2018
Publisher: John Wiley & Sons
Source: Cancer medicine, 2018, v. 7, no. 9, p. 4791-4800 How to cite?
Journal: Cancer medicine 
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.
URI: http://hdl.handle.net/10397/80003
ISSN: 2045-7634
DOI: 10.1002/cam4.1732
Rights: This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
The following publication Li, X. -., Zhang, S. -., Chiu, A. P., Lo, L. H., Huang, J., Rowlands, D. K., . . . Keng, V. W. (2018). Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor. Cancer Medicine, 7(9), 4791-4800 is available at https://dx.doi.org/10.1002/cam4.1732
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