Formononetin acts synergistically with a JAK2 inhibitor to suppress growth in myeloproliferative neoplasm by inhibiting JAK/STAT3 signaling pathway Article Swipe

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Huijun Jiang , Zaijing Fan , Jiashan Li , Xiaoqun Zheng ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.4314/tjpr.v22i6.2

Purpose: To determine the effect of formononetin (FMNT) in the proliferation, drug resistance, and DNA damage of myeloproliferative neoplasm (MPN), and to evaluate the potential of FMNT as a therapeutic target. Methods: Cell viability curves and colony formation assays were used to characterize the proliferation of HEL or HEL/R cells. Flow cytometry was conducted to assess the apoptosis of HEL or HEL/R cells, while western blotting was performed to evaluate the expressions of DNA H2AX, DNA-PK, and Rad51, which are indicative of DNA damage, and the phosphorylation levels of JAK2 and STAT3 were determined. Results: Formononetin (FMNT) suppressed cell proliferation of HEL cells in a dose-dependent manner. It significantly reduced colony formation and promoted apoptosis of HEL cells (p < 0.05). For HEL/R cells, FMNT treatment significantly reduced cell viability, and resistance, and promoted apoptosis. Moreover, FMNT elevated H2AX levels and significantly reduced the expressions of DNA-PK and Rad51 in TG101209 (TG)-induced JAK-TKI-resistant cells (p < 0.05). Furthermore, FMNT decreased JAK2 and STAT3 phosphorylation in JAK- TKI-resistant cells. Conclusion: Treatment with FMNT represses proliferation, promotes apoptosis, weakens JAK-TKI resistance, and strengthens DNA damage in MPN cells by suppressing JAK/STAT3 pathway. This suggests that FMNT is a potential therapeutic candidate for the treatment of MPN.

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Apoptosis Cell growth Viability assay Cancer research STAT3 Flow cytometry Formononetin Molecular biology Biology Chemistry Biochemistry Endocrinology Genistein Daidzein

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Type: article
Language: en
Landing Page: https://doi.org/10.4314/tjpr.v22i6.2
PDF: https://www.ajol.info/index.php/tjpr/article/download/250683/237003
OA Status: gold
Cited By: 2
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OpenAlex ID: https://openalex.org/W4386259405

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DOI: https://doi.org/10.4314/tjpr.v22i6.2

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Title: Formononetin acts synergistically with a JAK2 inhibitor to suppress growth in myeloproliferative neoplasm by inhibiting JAK/STAT3 signaling pathway

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Type: article

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Language: en

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Publication year: 2023

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Publication date: 2023-07-12

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Authors: Huijun Jiang, Zaijing Fan, Jiashan Li, Xiaoqun Zheng

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Concepts: Apoptosis, Cell growth, Viability assay, Cancer research, STAT3, Flow cytometry, Formononetin, Molecular biology, Biology, Chemistry, Biochemistry, Endocrinology, Genistein, Daidzein

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Cited by: 2

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abstract_inverted_index.suppressing	187
abstract_inverted_index.therapeutic	29, 197
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abstract_inverted_index.Formononetin	95
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