Attenuation of doxorubicin-induced cardiotoxicity by cryptotanshinone detected through association analysis of transcriptomic profiling and KEGG pathway

Abstract

Objective: The cardiotoxicity of doxorubicin (DOX) reduces the quality of life and prognosis of cancer patients, and therefore its clinical application has been largely restricted. This study aimed to assess the effects of cryptotanshione (CPT) on DOX-induced rat cardiac insufficiency. Results: CPT treatment significantly suppressed apoptosis in vitro. The oral administration of CPT significantly improved cardiac function in the rat model, reduced collagen production and suppressed apoptosis and the production of reactive oxygen species in the heart tissue. Transcriptomic profiling and its relevant bioinformatics analysis showed that CPT suppressed doxorubicin-induced cardiotoxicity by inhibiting p53 signaling pathway. Conclusion: Transcriptomic profiling and bioinformatics analysis can be used to evaluate the cardio-protective effect of CPT through inactivating p53 signaling pathway in the doxorubicin-mediated myocardial damage model. Methods: F-actin staining and flow cytometry were used to assess the effects of CPT on cardiomyocytes. In vivo, echocardiography and hemodynamic evaluation were used to assess the effects of CPT on the cardiac dysfunction in rats. Furthermore, transcriptomic profiling and bioinformatics analysis, as well as western blot analysis, were used to determine that CPT induced changes in the signaling pathways in the model.

Pharmacogenetics of Drug Metabolism: The Role of Gene Polymorphism in the Regulation of Doxorubicin Safety and Efficacy

“…The combined application of Dox with epigenetic drugs, either as mixed solutions or encapsulated agents in nanogels, was found to be more efficient than the drug alone [ 96 ]. The use of nanocarriers (nanoparticles (NPs)), including liposomes, polymers, electro-sprayed particles, and nanosuspensions, was suggested as a promising approach to minimize adverse side effects of Dox [ 19 , 20 , 102 , 105 , 106 , 107 , 108 , 109 ]. Several types of NPs were found to improve the pharmacokinetic characteristics of anti-cancer agents and provide better targeted delivery and controlled release into cancer cells [ 19 , 105 , 106 , 107 ].…”

“…The use of nanocarriers (nanoparticles (NPs)), including liposomes, polymers, electro-sprayed particles, and nanosuspensions, was suggested as a promising approach to minimize adverse side effects of Dox [ 19 , 20 , 102 , 105 , 106 , 107 , 108 , 109 ]. Several types of NPs were found to improve the pharmacokinetic characteristics of anti-cancer agents and provide better targeted delivery and controlled release into cancer cells [ 19 , 105 , 106 , 107 ]. Improved pharmacokinetic parameters were demonstrated for liposome-incorporated Dox [ 19 , 106 ].…”

“…Delivery of Dox by nanocarriers extended the drug plasma half-life and slowed its clearance without increases in gastrointestinal toxicity and cardiotoxicity [ 110 ]. Non-pegylated and pegylated liposomal Dox forms were approved for clinical treatment [ 20 , 105 , 106 , 107 , 108 , 109 ]. Application of nanotechnology may provide a solution for those patients with genetic polymorphism in CYP450 and/or MDR1 genes, although the degree of success with NP-loaded Dox/miRs remains to be assessed.…”

Cryptotanshinone Attenuated Pathological Cardiac Remodeling In Vivo and In Vitro Experiments

“…CTS treatment could markedly reduce atherosclerotic plaque formation and enhance plaque stability in ApoE-/-mice via inhibiting reactive oxygen species (ROS) production and NF-κB activation [4]. CTS treatment significantly depressed doxorubicin induced ROS production and cardiomyocyte apoptosis via suppressing p53 signaling pathway [9]. In addition, CTS administration could effectively attenuate diabetic cardiomyopathy associated cardiac fibrosis by reducing matrix metalloproteinase-9 (MMP-9) and connective tissue growth factor (CTGF) production via inhibiting STAT3 activity [10].…”

Cryptotanshinone ameliorates cardiac injury and cardiomyocyte apoptosis in rats with coronary microembolization

“…Accumulating evidences have demonstrated that CTS protected against coronary heart disease (CHD), angina pectoris and myocardial damages (Ding et al, 2019;L. Li et al, 2020;.…”