Wogonoside impedes the progression of acute myeloid leukemia through inhibiting bone marrow angiogenesis.

Abstract

Decreasing bone marrow (BM) microvessel density and circulating angiogenic cytokine levels are promising strategies for the treatment of relapsed and resistant acute myeloid leukemia (AML). Previous studies have reported that wogonoside could inhibit the progression of AML and suppress angiogenesis in a solid tumor, but the correlation of these two effects was ignored. In this research, we determined whether wogonoside could inhibit angiogenesis in this hematologic malignancy. We found that wogonoside could inhibit tumor growth and progression, and prolong the survival of nude mice inoculated with U937/MDR. Besides, reducing BM angiogenesis might cause therapeutic effect against resistant AML. Therefore, coculture between AML cells and BM stromal cells was established to imitate their crosstalk. Then, the effect of wogonoside on BM angiogenesis was tested in vitro and in vivo. We found that wogonoside could suppress microvessel formation in the chicken chorioallantoic membrane assay model and matrigel plug assay. The mechanism research revealed that wogonoside could block the JAK2-STAT3 pathway in AML cells and stromal cells to break their positive feedback. We detected several cytokines related to AML or angiogenesis and found that secreted interleukin-8 was a significant angiogenic cytokine to induce BM angiogenesis. These findings supported that new diagnostics and promising treatment strategies could be developed in relapsed and resistant AML patients.

• Authors: Binyan Lin, Kai Zhao, Dawei Yang, Dongsheng Bai, Yan Liao, Yuxin Zhou, Zhou Yu, Xiaoxuan Yu, Qinglong Guo, Na Lu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 2 Pg. 1913-1924 (02 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30105796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Angiogenesis Inhibitors
• CXCL8 protein, human
• Flavanones
• Glucosides
• Interleukin-8
• Janus Kinase Inhibitors
• STAT3 Transcription Factor
• STAT3 protein, human
• JAK2 protein, human
• Janus Kinase 2
• wogonoside

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Bone Marrow (blood supply)
• Chick Embryo
• Chorioallantoic Membrane (blood supply)
• Coculture Techniques
• Female
• Flavanones (pharmacology)
• Glucosides (pharmacology)
• Humans
• Interleukin-8 (metabolism)
• Janus Kinase 2 (antagonists & inhibitors, metabolism)
• Janus Kinase Inhibitors (pharmacology)
• Leukemia, Myeloid, Acute (drug therapy, metabolism, pathology)
• Mice, Inbred BALB C
• Mice, Inbred NOD
• Mice, Nude
• Mice, SCID
• Neovascularization, Pathologic
• Neovascularization, Physiologic (drug effects)
• Paracrine Communication (drug effects)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• Stromal Cells (drug effects, metabolism, pathology)
• Tumor Cells, Cultured
• U937 Cells
• Xenograft Model Antitumor Assays