Low dose amiodarone reduces tumor growth and angiogenesis
Eliana Steinberg1, Arnon Fluksman1, Chalom Zemmour1
1The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Abstract:
Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug's harmful side effects.
Insights
Low-dose Amiodarone effectively reduced glioblastoma tumor size and inhibited angiogenesis. This suggests dual anti-cancer properties, offering potential for safer therapeutic applications.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Amiodarone, an anti-arrhythmic drug, shows pre-clinical anti-cancer cytotoxicity.
- Severe side effects limit Amiodarone's clinical use.
- Tumor angiogenesis is crucial for tumor growth and metastasis.
Purpose of the Study:
- To investigate Amiodarone's effects on glioblastoma multiforme (GBM) tumor growth and angiogenesis.
- To explore potential dual anti-cancer mechanisms of Amiodarone.
- To assess Amiodarone's efficacy in a murine tumor model.
Main Methods:
- In vitro assays with U-87 MG glioblastoma cells and endothelial cells.
- In vivo studies using three murine models with GBM xenografts.
- Evaluation of tumor size, cytotoxicity, and angiogenic markers.
Main Results:
- Low-dose Amiodarone significantly reduced GBM xenograft tumor size.
- Amiodarone demonstrated a strong anti-angiogenic effect.
- Dual cytotoxic and anti-angiogenic properties were observed.
Conclusions:
- Amiodarone exhibits dual anti-cancer properties by directly reducing tumor size and inhibiting angiogenesis.
- Low-dose Amiodarone may offer a safer therapeutic window for cancer treatment.
- Further research is warranted to explore Amiodarone's clinical potential as an anti-cancer agent.
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