Related Experiment Video
Updated: Jun 23, 2025
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
Muscone abrogates breast cancer progression through tumor angiogenic suppression via VEGF/PI3K/Akt/MAPK signaling
Danhong Wang1,2,3, Xiaozhen Liu2,3, Weimin Hong4,2,3
1College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310014, Zhejiang, China.
Background:
Angiogenesis strongly reflects poor breast cancer outcome and an important contributor to breast cancer (BC) metastasis; therefore, anti-angiogenic intervention is a potential tool for cancer treatment. However, currently used antibodies against vascular endothelial growth factor A (VEGFA) or inhibitors that target the VEGFA receptor are not effective due to weak penetration and low efficiency. Herein, we assessed the anti-BC angiogenic role of muscone, a natural bioactive musk constituent, and explored possible anti-cancer mechanisms of this compound.
Methods:
CCK-8, EdU, scratch and Transwell assessments were employed to detect the muscone-mediated regulation of breast cancer (BC) and human umbilical vein endothelial cells (HUVECs) proliferation and migration. Tube formation, matrigel plug assay and zebrafish assay were employed for assessment of regulation of tumor angiogenesis by muscone. In vivo xenograft mouse model was constructed to compare microvessel density (MVD), vascular leakage, vascular maturation and function in muscone-treated or untreated mice. RNA sequencing was performed for gene screening, and Western blot verified the effect of the VEGFA-VEGFR2 pathway on BC angiogenic inhibition by muscone.
Results:
Based on our findings, muscone suppressed BC progression via tumor angiogenic inhibition in cellular and animal models. Functionally, muscone inhibited BC cell proliferation and migration as well as tumor cell-conditioned medium-based endothelial cell proliferation and migration. Muscone exhibited a strong suppressive influence on tumor vasculature in cellular and animal models. It abrogated tumor cell growth in a xenograft BC mouse model and minimized tumor microvessel density and hypoxia, and increased vascular wall cell coverage and perfusion. Regarding the mechanism of action, we found that muscone suppressed phosphorylation of members of the VEGF/PI3K/Akt/MAPK axis, and it worked synergistically with a VEGFR2 inhibitor, an Akt inhibitor, and a MAPK inhibitor to further inhibit tube formation.
Conclusion:
Overall, our results demonstrate that muscone may proficiently suppress tumor angiogenesis via modulation of the VEGF/PI3K/Akt/MAPK axis, facilitating its candidacy as a natural small molecule drug for BC treatment.
Insights
Muscone, a natural compound, effectively inhibits breast cancer progression by suppressing tumor angiogenesis. It targets the VEGF/PI3K/Akt/MAPK pathway, showing potential as a novel small molecule drug for breast cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Angiogenesis is crucial for breast cancer (BC) metastasis and outcome.
- Current anti-angiogenic therapies targeting vascular endothelial growth factor A (VEGFA) have limitations.
- Muscone, a natural musk compound, was investigated for its anti-angiogenic and anti-cancer effects in BC.
Purpose of the Study:
- To assess the anti-angiogenic role of muscone in breast cancer.
- To explore the anti-cancer mechanisms of muscone.
- To evaluate muscone as a potential therapeutic agent for breast cancer.
Main Methods:
- Cell proliferation, migration, and tube formation assays were used.
- In vivo studies included matrigel plug, zebrafish, and xenograft mouse models.
- RNA sequencing and Western blot analysis were performed to elucidate mechanisms.
Main Results:
- Muscone inhibited breast cancer cell proliferation and migration.
- It suppressed tumor angiogenesis, reducing microvessel density and hypoxia in vivo.
- Muscone modulated the VEGF/PI3K/Akt/MAPK signaling pathway.
Conclusions:
- Muscone demonstrates significant anti-angiogenic and anti-tumor effects in breast cancer models.
- Its mechanism involves the modulation of the VEGF/PI3K/Akt/MAPK axis.
- Muscone is a promising natural small molecule for breast cancer treatment.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:23Abnormal Proliferation
01:41Non-Canonical Wnt Signaling Pathways
02:54Canonical Wnt Signaling Pathway
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...