Two novel anticancer compounds with minimum cardiotoxic property
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(2020) 21:79
RESEARCH ARTICLE
Open Access
Two novel anticancer compounds with minimum cardiotoxic property Tayebeh Afsharirad1,2†, Raheleh Tahmasvand2†, Mohsen Amini3, Bahram Daraei1 and Mona Salimi2*
Abstract Background: Although two novel synthesized compounds with tri-aryl structures; 3-(4-chlorophenyl)-5-(4fluorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole (A) and 3,5-bis-(4-chlorophenyl)-4-phenyl-4,5-dihydro-1,2,4oxadiazole (B) have been previously demonstrated to possess remarkable anti-breast cancer activity, their cardiotoxicity remains a major concern due to their mechanism of action. To address this concern, we assessed the ability of these compounds to cause toxicity towards H9c2 cardiomyocytes as an in vitro model of cardiotoxicity. Methods: Cytotoxic activity of both compounds was explored in vitro on H9c2 cells using MTT assay. Annexin V/PI method, intracellular ROS determination and mitochondrial membrane potential assay were applied to elucidate the mechanism of action of the cell death. Results: MTT assay revealed a concentration- and time-dependent cardiotoxicity. Findings of apoptosis by double staining with annexin V and propidium iodide divulged no cell death including apoptosis and necrosis at the concentration that were effective to inhibit cancer cells proliferation (10 μM) at 24 and 48 h. Furthermore, flow cytometric measurement of membrane potential and ROS determination using DCFH-DA verified the safe concentration of the compounds against H9c2 cells with no cardiotoxic effect. However, the higher concentration of the compounds could induce cell death through ROS-mediated mitochondrial dysfunction. Conclusions: Altogether, the results represented two novel chemical molecules possessing anti-breast cancer activity with minimum cardiac side effect. Keywords: Cardiotoxicity, Apoptosis, ROS, Mitochondrial potential
Background Cardiovascular diseases (CVDs) remains number one of the fatal diseases, which is ever increasing worldwide and hence, scientific community has concerned about it [1, 2]. Cardiotoxicity occurs as a result of the complicated working of cardiac cells and tissues or due to a chemical molecule affecting heart function and structure [3, 4]. Cardiotoxicity induced by drugs has gained attention in the past few decades. In this context, anticancer * Correspondence: [email protected] † Tayebeh Afsharirad and Raheleh Tahmasvand contributed equally to this work. 2 Physiology and Pharmacology Department, Pasteur Institute of Iran, P.O. Box 13164, Tehran, Iran Full list of author information is available at the end of the article
therapy has a direct impact on cardiac function and the most common toxicities of heart are due to cancer treatment [5]. However, clinicians still use many cardiotoxic drugs due to their beneficial effects, which outweigh cardiac malformations risks [4]. As it was above-mentioned, most of the anticancer drugs exhibit a wide range of cardiovascular toxicities which results in stopping cancer treatment and affects the short- and long-term quality of
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