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A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells
Wu, Ke-Jia1; Huang, Jie-Min1; Zhong, Hai-Jing1; Dong, Zhen-Zhen2; Vellaisamy, Kasipandi2; Lu, Jin-Jian1; Chen, Xiu-Ping1; Chiu, Pauline3,4; Kwong, Daniel W. J.2; Han, Quan-Bin5; Ma, Dik-Lung2; Leung, Chung-Hang1
2017-06
Source PublicationPLOS ONE
ISSN1932-6203
Volume12Issue:6
Abstract

The JAK2/STAT3 signaling pathway plays a critical role in tumorigenesis, and has been suggested as a potential molecular target for anti-melanoma therapeutics. However, few JAK2 inhibitors were being tested for melanoma therapy. In this study, eight amentoflavone analogues were evaluated for their activity against human malignant melanoma cells. The most potent analogue, compound 1, inhibited the phosphorylation of JAK2 and STAT3 in human melanoma cells, but had no discernible effect on total JAK2 and STAT3 levels. A cellular thermal shift assay was performed to identify that JAK2 is engaged by 1 in cell lysates. Moreover, compound 1 showed higher antiproliferative activity against human melanoma A375 cells compared to a panel of cancer and normal cell lines. Compound 1 also activated caspase-3 and cleaved PARP, which are markers of apoptosis, and suppressed the antiapoptotic Bcl-2 level. Finally, compound 1 induced apoptosis in 80% of treated melanoma cells. To our knowledge, compound 1 is the first amentoflavone-based JAK2 inhibitor to be investigated for use as an anti-melanoma agent.

DOI10.1371/journal.pone.0177123
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000402611800006
PublisherPUBLIC LIBRARY SCIENCE
The Source to ArticleWOS
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Cited Times [WOS]:16   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
3.Department of Chemistry, The University of Hong Kong, Hong Kong, China
4.The State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong, China
5.School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wu, Ke-Jia,Huang, Jie-Min,Zhong, Hai-Jing,et al. A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells[J]. PLOS ONE,2017,12(6).
APA Wu, Ke-Jia.,Huang, Jie-Min.,Zhong, Hai-Jing.,Dong, Zhen-Zhen.,Vellaisamy, Kasipandi.,...&Leung, Chung-Hang.(2017).A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells.PLOS ONE,12(6).
MLA Wu, Ke-Jia,et al."A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells".PLOS ONE 12.6(2017).
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