ICG-001 suppressed doxorubicin-induced cardiotoxicity in vitro and in vivo comparably to dexrazoxane, while also exhibiting cytotoxicity to cancer cells.
Does ICG-001 prevent doxorubicin-induced cardiotoxicity and enhance cancer cytotoxicity in preclinical models?
ICG-001 demonstrates potential as a dual-action adjunct to doxorubicin by protecting cardiomyocytes from toxicity while simultaneously enhancing cancer cytotoxicity.
Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell-derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.
Wu et al. (Fri,) conducted a other in Doxorubicin-induced cardiotoxicity. ICG-001 vs. Dexrazoxane was evaluated on Suppression of doxorubicin-induced cardiotoxicity and cancer cytotoxicity. ICG-001 suppressed doxorubicin-induced cardiotoxicity in vitro and in vivo comparably to dexrazoxane, while also exhibiting cytotoxicity to cancer cells.
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