Curcumin promotes oxidative stress, apoptosis and autophagy in H9c2 rat cardiomyoblasts

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ORIGINAL ARTICLE

Curcumin promotes oxidative stress, apoptosis and autophagy in H9c2 rat cardiomyoblasts Iván Zepeda‑Quiróz1,2 · Helen Sánchez‑Barrera1 · Zaira Colín‑Val1 · Diana Xochiquetzal Robledo‑Cadena3 · Sara Rodríguez‑Enríquez3 · Rebeca López‑Marure1 Accepted: 31 August 2020 © The Korean Society of Toxicogenomics and Toxicoproteomics 2020 2020

Abstract Background  Curcumin, a polyphenol derived from Curcuma longa, has some adverse effects on heart; however, its toxic effects on cardiac cells are poorly understood. Objective  To evaluate the toxicity of curcumin on H9c2 rat cardiomyoblasts. To this, H9c2 cells were exposed to different concentrations of curcumin and proliferation, viability, cell cycle, oxidative stress, mitochondrial membrane potential (ΔΨm), death and autophagy were evaluated. Results  Curcumin caused concentration-dependent inhibition of H9c2 cells proliferation and viability. A higher sub-G1 population was observed in cells treated with curcumin, which was related with phosphatidylserine translocation and increase of activated caspase-9, indicating apoptotic death. Curcumin induced oxidative stress and decreased ΔΨm causing mitochondrial dysfunction. Additionally, it promoted autophagy, revealed by higher LC3B and beclin-1 protein expression and mitophagy. Conclusion  Curcumin exhibited toxic effects in cardiac cells and further studies are required to validate its therapeutic potential and use as anti-inflammatory and anti-oxidant agent in the cardiovascular system.

* Rebeca López‑Marure [email protected] 1



Departamento de Fisiología, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano No. 1, Colonia Sección 16, Tlalpan, 14080 Ciudad de México, México

2



Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México

3

Departamento de Bioquímica, Instituto Nacional de Cardiología “Ignacio Chávez”, Ciudad de México, México



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Molecular & Cellular Toxicology

Graphic abstract

Keywords  Curcumin · Cardiomyoblasts · Cell cycle · Oxidative stress · Cell death · Mitochondrial damage · Autophagy · Mitophagy Abbreviations ROS Reactive oxygen species H2DCFDA 2,7-Dichlorodihydrofluorescein diacetate Rh123 Rhodamine 123 ΔΨm Mitochondrial membrane potential LC3 Microtubule-associated protein 1A/1B-light chain 3

Introduction The compound curcumin (diferuloylmethane), isolated from the rhizome of Curcuma longa (Jayaprakasha et al. 2005), shows beneficial effects on diseases where an inflammatory process is involved such as cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer’s disease, psoriasis, among others (Pari et al. 2008). It has been established that the cellular protection induced by curcumin might be due in part to its ability to modulate the immune system (Anderson et al.

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2007), as well as from its anti-inflammatory effect. This last, modulating the activation of T and B cells, macrophages, neutrophils, natural killer cells, and dendritic cells; but also, curcumin can af