Monensin Inhibits Anaplastic Thyroid Cancer <i>via</i> Disrupting Mitochondrial Respiration and AMPK/mTOR Signaling

Author(s):

Yanli Li, Qianshu Sun, Sisi Chen, Xiongjie Yu and Hongxia Jing*   Pages 2539 - 2547 ( 9 )

Abstract:

<p>Objective: The clinical management of anaplastic thyroid cancer (ATC) remains challenging, and novel treatment methods are needed. Monensin is a carboxyl polyether ionophore that potently inhibits the growth of various cancer types. Our current work investigates whether monensin has selective anti-ATC activity and systematically explores its underlying mechanisms. <p> Methods: Proliferation and apoptosis assays were performed using a panel of thyroid cancer cell lines. Mitochondrial biogenesis profiles, ATP levels, oxidative stress, AMPK, and mTOR were examined in these cells after monensin treatment. <p> Results: Monensin is effective in inhibiting proliferation and inducing apoptosis in a number of thyroid cancer cell lines. The results are consistent across cell lines of varying cellular origins and genetic mutations. Compared to other thyroid cancer cell types, ATC cell lines are the most sensitive to monensin. Of note, monensin used at our experimental concentration affects less of normal cells. Mechanistic studies reveal that monensin acts on ATC cells by disrupting mitochondrial function, inducing oxidative stress and damage, and AMPK activation-induced mTOR inhibition. We further show that mitochondrial respiration is a critical target for monensin in ATC cells. <p> Conclusions: Our pre-clinical findings demonstrate the selective anti-ATC activities of monensin. This is supported by increasing evidence that monensin can be repurposed as a potential anti-cancer drug.</p>

Keywords:

Monensin, mitochondria, oxidative stress, thyroid cancer, AMPK, mTOR.

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