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Resveratrol selectively induces apoptosis in malignant cells with the JAK2V617F mutation by inhibiting the JAK2 pathway
Author(s) -
Trung Ly Quoc,
Espinoza J. Luis,
An Dao T.,
Viet Nguyen Hoang,
Shimoda Kazuya,
Nakao Shinji
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500166
Subject(s) - resveratrol , janus kinase 2 , cancer research , apoptosis , chemistry , ruxolitinib , stat3 , kinase , biology , myelofibrosis , biochemistry , immunology , bone marrow
Scope Resveratrol is a natural occurring polyphenol with several health promoting activities, including anticancer potential. Here, we analyzed the cytotoxic effects of resveratrol against malignant cells characterized by aberrant activation of the Janus kinase 2 (JAK2). Methods and results Cell‐cycle analysis, proliferation, apoptosis, and Western blotting assays were performed to study the effect of resveratrol on malignant cells exhibiting an excessive activation of the JAK2 pathway secondary to the JAK2 V617F mutation. Resveratrol inhibited proliferation and induced apoptosis in JAK2 V617F mutant tumor cells and its selectivity was 1.5–6.9 times greater than that observed in other tumor cells without the JAK2 V617F mutation. In addition, resveratrol inhibited the phosphorylation of JAK1, JAK2, and Tyk2 and their downstream mediators, including STAT3 and STAT5. In primary cultures, resveratrol treatment inhibited erythroid progenitor colony formation in blood samples obtained from JAK2 V617F polycythemia vera patients. Moreover, resveratrol synergized with the selective JAK2 inhibitor ruxolitinib, eliminating tumor cells with the JAK2 mutation. Conclusion Resveratrol may have therapeutic potential against myeloproliferative neoplasms associated with the aberrant activation of the JAK2 pathway.