Presentation Information
[P04-599]Dietary phytochemicals prevent Doxorubicin-induced cardiomyopathy targeting mitochondria
○HUI-CHEN CHUNG1, YA-HUI Chang4, SHU-MEI LIN3, SU-JUNG HSU2 (1. Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan (Taiwan), 2. Institute of Fisheries Science, National Taiwan University, Taipei City, Taiwan (Taiwan), 3. Department of Food Science, National Chiayi University, Chiayi City, Taiwan (Taiwan), 4. Chia-Yi Christian Hospital, Chiayi City, Taiwan (Taiwan))
Keywords:
doxorubicin cardiotoxicity,mitochondria,stilbene compounds
Doxorubicin (DOX) is a chemotherapeutic drug widely used for cancer treatment; however, its clinical application is limited by cardiotoxicity. Although free radicals generated from redox cycling and free cellular iron have been proposed as the predominant primary pathogenic mechanisms, the precise molecular mechanism underlying DOX-induced cardiotoxicity remains incompletely understood. Great efforts have been devoted to developing strategies to prevent these toxic side effects. Accumulating evidence suggests that mitochondria are key determinants and potential therapeutic targets in DOX-induced cardiomyopathy.
In this study, the protective effects of dietary phytochemicals, including stilbene compounds found in peanuts—arachidin-1 (Ara-1), arachidin-3 (Ara-3), isopentadienyl resveratrol (IPD), and resveratrol (Rev), as well as Oolong tea extract against DOX-induced cardiotoxicity were examined using the H9c2 rodent cardiac myoblast model, with a focus on mitochondrial modulation.
The results indicated that DOX treatment reduced cell viability, which was associated with mitochondrial injury characterized by dysregulation of mitochondrial mass, morphological dynamics, membrane potential, reactive oxygen species (ROS) production, cellular apoptosis, and autophagy. Supplementation with stilbene compounds or Oolong tea extract exerted protective effects against DOX-induced toxicity by regulating mitochondrial dynamics and function in cardiomyocytes. These treatments protected cardiac myoblasts from DOX-induced cytotoxicity by maintaining mitochondrial membrane potential at normal levels and inhibiting apoptosis. Animal experiments further demonstrated that stilbene compounds from peanuts exhibited no detectable toxicity in any tested organ in mice inoculated with 4T1 breast cancer cells and concurrently administered DOX. Importantly, these stilbene compounds did not compromise the anticancer efficacy of DOX but significantly reduced DOX-induced cardiac tissue damage. Furthermore, miRNA microarray analyses revealed that the cardioprotective mechanism of stilbene compounds is associated with the regulation of miRNAs known to be involved in the pathogenesis of various types of cardiac injury.
Overall, the results of this study suggest that cardiac mitochondria are potential therapeutic targets for DOX-induced cardiotoxicity. Phytochemicals that modulate mitochondrial function may therefore serve as promising dietary supplements or adjuvant agents for cancer chemotherapy with DOX.
In this study, the protective effects of dietary phytochemicals, including stilbene compounds found in peanuts—arachidin-1 (Ara-1), arachidin-3 (Ara-3), isopentadienyl resveratrol (IPD), and resveratrol (Rev), as well as Oolong tea extract against DOX-induced cardiotoxicity were examined using the H9c2 rodent cardiac myoblast model, with a focus on mitochondrial modulation.
The results indicated that DOX treatment reduced cell viability, which was associated with mitochondrial injury characterized by dysregulation of mitochondrial mass, morphological dynamics, membrane potential, reactive oxygen species (ROS) production, cellular apoptosis, and autophagy. Supplementation with stilbene compounds or Oolong tea extract exerted protective effects against DOX-induced toxicity by regulating mitochondrial dynamics and function in cardiomyocytes. These treatments protected cardiac myoblasts from DOX-induced cytotoxicity by maintaining mitochondrial membrane potential at normal levels and inhibiting apoptosis. Animal experiments further demonstrated that stilbene compounds from peanuts exhibited no detectable toxicity in any tested organ in mice inoculated with 4T1 breast cancer cells and concurrently administered DOX. Importantly, these stilbene compounds did not compromise the anticancer efficacy of DOX but significantly reduced DOX-induced cardiac tissue damage. Furthermore, miRNA microarray analyses revealed that the cardioprotective mechanism of stilbene compounds is associated with the regulation of miRNAs known to be involved in the pathogenesis of various types of cardiac injury.
Overall, the results of this study suggest that cardiac mitochondria are potential therapeutic targets for DOX-induced cardiotoxicity. Phytochemicals that modulate mitochondrial function may therefore serve as promising dietary supplements or adjuvant agents for cancer chemotherapy with DOX.
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