Molecular effects of genistein, as a potential anticancer agent, on CXCR-4 and VEGF pathway in acute lymphoblastic leukemia

Background Vascular endothelial growth factor (VEGF) is one of the angiogenic mediators that can be secreted by leukemic cells and plays an important role in tumor invasion and metastasis. Another important agent contributing to the relapse of ALL is C-X-C chemokine receptor type-4 (CXCR-4), express...

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Published in:Molecular biology reports 2022-06, Vol.49 (6), p.4161-4170
Main Authors: Shahmoradi, Mohsen, Banisharif-Dehkordi, Fatemeh, kouhihabibidehkordi, Mahnoush, GhatrehSamani, Mahdi, Jami, Mohammad-Saied, Shirzad, Hedayatollah, Pourgheysari, Batoul
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Angiogenesis
Animal Anatomy
Animal Biochemistry
Antitumor agents
Biomedical and Life Sciences
Cell culture
Cell surface
Cell viability
Chemokine receptors
Colorimetry
Cytotoxicity
Flow cytometry
Gene expression
Genistein
Histology
Leukemia
Life Sciences
Metastases
Metastasis
Molting
Morphology
Original Article
Tumors
Vascular endothelial growth factor
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Summary:Background Vascular endothelial growth factor (VEGF) is one of the angiogenic mediators that can be secreted by leukemic cells and plays an important role in tumor invasion and metastasis. Another important agent contributing to the relapse of ALL is C-X-C chemokine receptor type-4 (CXCR-4), expression of this receptor in cancer cells has been related to metastasis. It has been identified that genistein—a soy-derived isoflavonoid—has anti-angiogenesis functions. We aimed to show the effects of this compound on VEGF and CXCR-4 in Acute lymphoblastic leukemia (ALL) cell models. Methods and results The cytotoxicity of Genistein was measured using the MTS colorimetric assay. After being treated with Genistein, the expression of VEGF in mRNA and protein levels was measured in MOLT-4 and Jurkat cells. We also used flow cytometry assay to determine the expression of CXCR-4 in cell surfaces. We found that Genistein decreased cell viability in two cell models while was more effective on MOLT-4 cells. After Genistein-treatment, surface expression levels of CXCR-4 were decreased, while VEGF secretion and mRNA expression levels were increased in MOLT-4 and Jurkat cells. Conclusions The results suggest that Genistein may not be a reliable choice for the treatment of ALL; however, this different identified pattern can be useful for the recognition of VEGF and CXCR-4 modulators and thus for planning new treatments for leukemia and other VEGF related disorders.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-022-07163-0