Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients

Chang, Wei Ting; Lin, Yu Wen; Ho, Chung Han; Chen, Zhih Cherng; Liu, Ping Yen; Shih, Jhih Yuan

doi:10.1007/s00204-020-02951-8

Cited by 36 publications

(32 citation statements)

References 22 publications

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“…The present study showed that WG reversed the opening of mPTP and reduced the release of apoptotic factors cytochrome c into the cytoplasm, so as to prevent apoptosis. DOX can directly activate cardiomyocyte apoptosis by reducing Bcl-2/Bax ratio ( 49 ). Previous studies have noted that the high expression of Bcl-2 can enhance the resistance of cells to most DNA damage factors and inhibit the apoptosis of target cells caused by most chemotherapeutic drugs and that the Bax gene, which inhibits Bcl-2, is the main apoptosis gene in human body ( 50 , 51 ).…”

Section: Discussionmentioning

confidence: 99%

Wogonin reduces cardiomyocyte apoptosis from mitochondrial release of cytochrome c to improve doxorubicin‑induced cardiotoxicity

et al. 2022

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Doxorubicin (DOX) has powerful anticancer properties, but its clinical application is affected by its serious cardiotoxicity. Wogonin (WG) has been shown to have marked cardiovascular protection potential. However, it is not known whether this potential can protect the heart from DOX damage. The aim of the present study was to investigate whether WG could ameliorate the cardiotoxicity of DOX. DOX and WG were used to establish a model of cardiac damage. Echocardiography, brain natriuretic peptide, creatine kinase MB and cardiac troponin T were used to detect the degree of cardiac damage. The levels of superoxide dismutase, malondialdehyde, glutathione and catalase in serum were measured to observed oxidative stress state. The mRNA levels of cyclophilin D, voltage-dependent anion-selective channel 1 and adenine nucleotide transporter 1 were detected by reverse transcription-quantitative PCR. Western blotting was used to detect the expression of cytochrome c in mitochondria and cytoplasm and cleaved-caspase-9 and pro/cleaved-caspase-3 in cytoplasm in cardiac tissue and primary cardiomyocytes to verify the related signaling pathways. DOX rats showed a series of cardiac damage. However, these damages were alleviated following WG treatment. Further studies showed that WG antagonized DOX cardiotoxicity through inhibiting the release of cytochrome c. WG protected rat heart from DOX damage. The mechanism may be closely related to inhibiting the release of cytochrome c from mitochondria and reducing cardiomyocyte apoptosis caused by caspase activation.

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Section: Discussionmentioning

confidence: 99%

Wogonin reduces cardiomyocyte apoptosis from mitochondrial release of cytochrome c to improve doxorubicin‑induced cardiotoxicity

et al. 2022

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“…Indeed, Dapa has decreased the cardiac expression of cleaved caspase-3 and protected against doxorubicin-induced cardio-toxicity in breast cancer patients [ 34 ]. In pre-ischemia, Dapa conferred the maximum level of cardio-protection through decreasing cardiac apoptosis and caspase-3 expression [ 35 ], as well as attenuated experimental inflammatory bowel disease in rats and dampened colonic apoptosis by lowering the caspase-3 activity and cleaved caspase-3 expression [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation

El-Sherbiny

El-Shafey

Said

et al. 2022

Life

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In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune–histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury.

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“…It has been reported that dapagliflozin protects against doxorubicin-induced cardiotoxicity in patients with breast cancer and diabetes. Moreover, dapagliflozin inhibits doxorubicin-induced myocardial fibrosis and greatly improves cardiac function by inhibiting the apoptosis of cardiomyocytes and the generation of ROS ( 122 ). Therefore, topoisomerase inhibitors and dapagliflozin can protect the heart from the toxicity of chemotherapy drugs by inhibiting myocardial remodeling.…”

Section: Prevention Strategiesmentioning

confidence: 99%

Mechanism and prevention strategy of a bidirectional relationship between heart failure and cancer (Review)

et al. 2021

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Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients

Cited by 36 publications

References 22 publications

Wogonin reduces cardiomyocyte apoptosis from mitochondrial release of cytochrome c to improve doxorubicin‑induced cardiotoxicity

Wogonin reduces cardiomyocyte apoptosis from mitochondrial release of cytochrome c to improve doxorubicin‑induced cardiotoxicity

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation

Mechanism and prevention strategy of a bidirectional relationship between heart failure and cancer (Review)

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