Low dose amiodarone reduces tumor growth and angiogenesis

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.

Potassium channel-driven bioelectric signalling regulates metastasis in triple-negative breast cancer

“…Nevertheless, we show that the depolarization produced by amiodarone treatment results in reduced TNBC cell migration and metastasis, demonstrating that the cellular RMP is a targetable feature of TNBC cells that can be exploited to treat metastasis. Importantly, our results demonstrate that the anti-cancer effects of amiodarone can be achieved with lower doses than the equivalent standard therapeutic levels used for cardiac indications, 78 , 79 avoiding previously reported off-target toxicity. 80 , 81 Ion channel blockers such as amiodarone present a rich resource for drug repurposing due to their ubiquity and known safety profiles.…”

Risk of Glioblastoma Multiforme in Patients Taking Ion Channel Blockers

“…Amiodarone is an anti-arrhythmic that can block voltage-gated potassium, calcium, and sodium channels. This drug has also been shown to reduce glioblastoma growth in vivo by exhibiting direct anti-cancer effects and antiangiogenic activity [18,19]. As such, some anti-tumorigenic effects of amiodarone are likely due to its inhibition of ion channels, which inhibit tumor cell proliferation and migration and its effect on angiogenesis.…”