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.
Highlights
Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985
We propose that low dose Amiodarone possesses both anti-cancer and anti-angiogenic activity that should be explored further as a potential candidate for combating highly vascularized tumors
Cells were seeded in the upper compartment containing 1% fetal calf serum (FCS) and were allowed to migrate to the underside of this higher compartment which contained 10% FCS
Summary
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, making it a potential candidate for use as an anti-cancer treatment. 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. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Pre-clinical studies suggest that Amiodarone can reverse multidrug resistance in several types of cancers and enhance cytotoxicity effects both as a single agent or in combination with other anti-cancer drugs[6,7,8,9], making it a potential candidate for anti-cancer treatment. The well-established angiogenesis in vivo models — the Matrigel plug assay and the corneal micropocket assay — showed that low dose Amiodarone, locally or systemically administered, markedly reduced blood vessel formation in addition to significantly suppressing GBM xenograft tumor growth associated with low tumor vascularization
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