Abstract: Cardiotoxicity is a major cause of high attrition rates among newly developed drugs. Moreover, anti-cancer treatment-induced cardiotoxicity is one of the leading reasons of mortality in cancer survivors. Cardiotoxicity screening in vitro may improve predictivity of cardiotoxicity by novel drugs, using human pluripotent stem cell (hPSC)-derived-cardiomyocytes. In addition, there is no good methods to predict the effects of long-term exposure to new drug candidates.
Human iPCS cardiomyocytes have become widely used in drug discovery screening as well as in cardiotoxicity. Detection by Ca2+ oscillation was the cheapest and most user-friendly methods. In the present study, we used hiPSC cardiomyocytes to check the effects of long-term exposure to anticancer drugs and HERG inhibitors on cardiomyocytes. By using hiPCS cardiomyocytes , we were able to detect long-term Ca2+ oscillation of typical anticancer drugs, such as Sunitinib, and the HERG inhibitor 17-AAG, for more than 10 days without staining with a fluorescent dye (N=5,Dose=6). The prolonged administration increased the sensitivity of the assessment.
The continued exposure revealed that the difference in cardiotoxicity. Arsenic(Ⅲ) trioxide was more evident after 6 days of treatment than with 3 days of treatment, suggesting that continued exposure improved the predictive power for cardiotoxicity of anti-cancer drugs.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly being used as instruments for disease modelling, drug discovery, and mechanistic toxicity studies. This method is a simple method to study the long-term effects of new drugs on iPSC cardiomyocytes by High throughput screening mode.
