| 2 | The antiangiogenic phloroglucinol hyperforin inhibits the secretion of proMMP-2, proMMP-9 and VEGF-A during apoptosis of primary acute myeloid leukemia cells显示文摘Aim:Angiogenesis is observed in acute myeloid leukemia(AML).AML cells abnormally proliferate and are resistant to death.Positive regulators of angiogenesis,VEGF-A and matrix metalloproteinases(MMPs)2 and 9 are markers of disease status in AML.The natural phloroglucinol hyperforin(HF)displays antitumoral properties of potential pharmacological interest.Herein,we investigated the effects of HF on MMP-2/9 and VEGF-A expression and survival of primary AML cells.Methods:Blood and bone marrow samples were collected in 45 patients with distinct subtypes defined by French American British classification,i.e.,M0,M1,M2,M3,M4,and M5.Levels of MMPs and VEGF-A in leukemic blood cells and culture supernatants were determined by RT-PCR,ELISA,and gelatin zymography(MMPs).The balance between cell death and survival was assessed by flow cytometry with analysis of phosphatidylserine externalization and caspase-3 activation.Results:The administration of HF promoted a caspase-associated apoptosis in primary AML blasts(from blood and bone marrow),but not normal blood cells and monocytes.In addition,HF inhibited the levels of secreted proMMP-2,proMMP-9,and VEGF-A without altering transcripts.The induction of apoptosis by HF significantly paralleled the inhibition of MMP-2/9 and VEGF-A release by HF.No differences were seen in response to the deleterious effects of HF between AML cells of distinct subtypes.Conclusion:Our results suggest that HF,through its proapoptotic and potential antiangiogenic properties(by inhibiting MMP-2/9 and VEGF-A)on primary AML cells,might be a useful experimental agent,in combination with existing drugs,for new therapeutic approaches in the treatment of this incurable disease. | Faten Merhi Ruoping Tang Ollivier Legrand Florence Nguyen-Khac Santos A.Susin Brigitte Bauvois | 2021 | Journal of Cancer Metastasis and Treatment2021，7，1： | 0 |
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