Anti-tumor effect of dandelion flavone on multiple myeloma cells and its mechanism
Background Multiple myeloma (MM) is a prevalent hematologic malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow and excessive monoclonal immunoglobulin production, leading to organ damage. Despite therapeutic advancements, recurrence and drug resi...
Saved in:
Published in | Discover. Oncology Vol. 15; no. 1; pp. 215 - 11 |
---|---|
Main Authors | , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
08.06.2024
Springer Nature B.V Springer |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Background
Multiple myeloma (MM) is a prevalent hematologic malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow and excessive monoclonal immunoglobulin production, leading to organ damage. Despite therapeutic advancements, recurrence and drug resistance remain significant challenges.
Objective
This study investigates the effects of dandelion flavone (DF) on MM cell proliferation, migration, and invasion, aiming to elucidate the mechanisms involved in MM metastasis and to explore the potential of traditional Chinese medicine in MM therapy.
Methods
DF's impact on myeloma cell viability was evaluated using the CCK-8 and colony formation assays. Cell mobility and invasiveness were assessed through wound healing and transwell assays, respectively. RT-PCR was employed to quantify mRNA levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Apoptotic rates and molecular markers were analyzed via flow cytometry and RT-PCR. The PI3K/AKT signaling pathway was studied using Western blot and ELISA, with IGF-1 and the PI3K inhibitor LY294002 used to validate the findings.
Results
DF demonstrated dose-dependent inhibitory effects on MM cell proliferation, migration, and invasion. It reduced mRNA levels of MMP-2 and MMP-9 while increasing those of TIMP-1 and TIMP-2. Furthermore, DF enhanced the expression of pro-apoptotic proteins and inhibited M2 macrophage polarization by targeting key molecules and enzymes. The anti-myeloma activity of DF was mediated through the inhibition of the PI3K/AKT pathway, as evidenced by diminished phosphorylation and differential effects in the presence of IGF-1 and LY294002.
Conclusion
By modulating the PI3K/AKT pathway, DF effectively inhibits MM cell proliferation, migration, and invasion, and induces apoptosis, establishing a novel therapeutic strategy for MM based on traditional Chinese medicine. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
ISSN: | 2730-6011 2730-6011 |
DOI: | 10.1007/s12672-024-01076-z |