Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity

Chen, Miao; Samuel, Vijaya Paul; Wu, Yi; Dang, Minyan; Lin, Yukiat; Sriramaneni, Raghava N.; Sah, Sushil Kumar; Chinnaboina, Gopala Krishna; Zhang, Guangping

doi:10.1615/jenvironpatholtoxicoloncol.2019029341

Cited by 22 publications

(14 citation statements)

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“…Genistein treatment induced Nrf2 and detoxification genes expression by activation/phosphorylation of MAPK‐ERK1/2 and PKC proteins (Zhai et al, 2013). It was reported that genistein protective effects on DOX‐induced cardiotoxicity in mice, were mediated by Nrf‐2/HO‐1 signaling (Z. Bai & Wang, 2019; M. Chen et al, 2019) (Figure 1).…”

Section: Ncs That Protected Against Dox‐induced Cardiotoxicity Via Acmentioning

confidence: 99%

Natural compounds against doxorubicin‐induced cardiotoxicity: A review on the involvement of Nrf2/ARE signaling pathway

Yarmohammadi

Rezaee

Karimi

2020

Phytotherapy Research

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Cardiotoxicity is the main concern for long-term use of the doxorubicin (DOX). Reactive oxygen species (ROS) generation leads to oxidative stress that significantly contributes to the cardiac damage induced by DOX. The nuclear factor erythroid 2-related factor (Nrf2) acts as a protective player against DOX-induced myocardial oxidative stress. Several natural compounds (NCs) with anti-oxidative effects, were examined to suppress DOX cardiotoxicity such as asiatic acid, α-linolenic acid, apigenin, baicalein, β-lapachone, curdione, dioscin, ferulic acid, Ganoderma lucidum polysaccharides, genistein, ginsenoside Rg3, indole-3-carbinol, naringenin-7-O-glucoside, neferine, p-coumaric acid, pristimerin, punicalagin, quercetin, sulforaphane, and tanshinone IIA. The present article, reviews NCs that showed protective effects against DOX-induced cardiac injury through induction of Nrf2 signaling pathway.

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Section: Ncs That Protected Against Dox‐induced Cardiotoxicity Via Acmentioning

confidence: 99%

Natural compounds against doxorubicin‐induced cardiotoxicity: A review on the involvement of Nrf2/ARE signaling pathway

Yarmohammadi

Rezaee

Karimi

2020

Phytotherapy Research

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“…Protected from chronic DOX in rats [190,229] and mice [185] in vivo. Augmented the cardioprotective effect of losartan against chronic DOX cardiotoxicity [230] Enhanced DOX anti-cancer effects in xenografts of leukemia P388 cells [185], liver cancer cells [231], 4T1 breast cancer cells [232,233] Reversed chemoresistance to DOX in hepatocellular carcinoma cells [202], breast cancer cells [200,212], prostate cancer cells [206], multidrug-resistant leukemia K562 cells [210] Enhanced chemotherapeutic effect of DOX against human breast cancer cells [195][196][197]199,234], human colorectal HT29 cancer cell line [208], neuroblastoma cells [235] Luteolin 79 [219] Protected against DOX-induced cardiomyocyte toxicity in vitro [188] Attenuated acute DOX-induced myocardial lipid peroxidation in vivo [236] Luteolin ( [240] Induced CYP1B1 gene expression [241,242] Protected from chronic DOX-induced cardiotoxicity in vivo [243,244] Protected from DOX-induced senescence in vascular smooth muscle cells [191] Potentiated the cytotoxic effect of DOX in MCF-7, MCF-7/ADR cells, MDA-MB-231 (breast), PC-3 (prostate), H460 (lung), and BxPC-3 (pancreas) cancer cells [213,[245][246][247]] Attenuated DOX-induced cytotoxicity in MCF-7 breast cancer cells in one study [248] Sensitized diffuse large cell lymphoma to CHOP (cyclophosphamide, DOX, vincristine, prednisone) chemotherapy in SCID tumor-bearing mice in vivo [2...…”

Section: Chemosensitizing Effects Of Cyp1b1 Inhibitorsmentioning

confidence: 99%

CYP1B1 as a therapeutic target in cardio-oncology

2020

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Cardiovascular complications have been frequently reported in cancer patients and survivors, mainly because of various cardiotoxic cancer treatments. Despite the known cardiovascular toxic effects of these treatments, they are still clinically used because of their effectiveness as anti-cancer agents. In this review, we discuss the growing body of evidence suggesting that inhibition of the cytochrome P450 1B1 enzyme (CYP1B1) can be a promising therapeutic strategy that has the potential to prevent cancer treatment-induced cardiovascular complications without reducing their anti-cancer effects. CYP1B1 is an extrahepatic enzyme that is expressed in cardiovascular tissues and overexpressed in different types of cancers. A growing body of evidence is demonstrating a detrimental role of CYP1B1 in both cardiovascular diseases and cancer, via perturbed metabolism of endogenous compounds, production of carcinogenic metabolites, DNA adduct formation, and generation of reactive oxygen species (ROS). Several chemotherapeutic agents have been shown to induce CYP1B1 in cardiovascular and cancer cells, possibly via activating the Aryl hydrocarbon Receptor (AhR), ROS generation, and inflammatory cytokines. Induction of CYP1B1 is detrimental in many ways. First, it can induce or exacerbate cancer treatment-induced cardiovascular complications. Second, it may lead to significant chemo/radio-resistance, undermining both the safety and effectiveness of cancer treatments. Therefore, numerous preclinical studies demonstrate that inhibition of CYP1B1 protects against chemotherapy-induced cardiotoxicity and prevents chemo- and radio-resistance. Most of these studies have utilized phytochemicals to inhibit CYP1B1. Since phytochemicals have multiple targets, future studies are needed to discern the specific contribution of CYP1B1 to the cardioprotective and chemo/radio-sensitizing effects of these phytochemicals.

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“…During conditions of oxidative stress, Nrf2 is activated, translocated to the nuclear region, and combined with the antioxidant response element located in the promoter region of phase II antioxidant enzyme genes, such as heme oxygenase 1 ( HO-1 ). It results in the detoxification of 4-hydroxylnonenal (4-HNE) and a decrease in ROS level, which releases the level of apoptosis [ 19 , 20 ]. In previous studies, it was found that DOX decreases the expression of Nrf2, resulting in an increase in oxidative stress and cell apoptosis [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Orosomucoid 1 Attenuates Doxorubicin-Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

Cheng

Liú

Xing

et al. 2020

BioMed Research International

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Doxorubicin (DOX) is an effective anticancer drug, but its therapeutic use is limited by its cardiotoxicity. The principal mechanisms of DOX-induced cardiotoxicity are oxidative stress and apoptosis in cardiomyocytes. Orosomucoid 1 (ORM1), an acute-phase protein, plays important roles in inflammation and ischemic stroke; however, the roles and mechanisms of ORM1 in DOX-induced cardiotoxicity remain unknown. Therefore, in the present study, we aimed to investigate the function of ORM1 in cardiomyocytes experiencing DOX-induced oxidative stress and apoptosis. A DOX-induced cardiotoxicity animal model was established in C57BL/6 mice by administering an intraperitoneal injection of DOX (20 mg/kg), and the control group was intraperitoneally injected with the same volume of sterilized saline. The effects were assessed after 7 d. Additionally, H9c2 cells were stimulated with DOX (10 μM) for 24 h. The results showed decreased ORM1 and increased oxidative stress and apoptosis after DOX stimulation in vivo and in vitro. ORM1 overexpression significantly reduced DOX-induced oxidative stress and apoptosis in H9c2 cells. ORM1 significantly increased the expression of nuclear factor-like 2 (Nrf2) and its downstream protein heme oxygenase 1 (HO-1) and reduced the expression of the lipid peroxidation end product 4-hydroxynonenal (4-HNE) and the level of cleaved caspase-3. In addition, Nrf2 silencing reversed the effects of ORM1 on DOX-induced oxidative stress and apoptosis in cardiomyocytes. In conclusion, ORM1 inhibited DOX-induced oxidative stress and apoptosis in cardiomyocytes by regulating the Nrf2/HO-1 pathway, which might provide a new treatment strategy for DOX-induced cardiotoxicity.

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Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity

Cited by 22 publications

References 0 publications

Natural compounds against doxorubicin‐induced cardiotoxicity: A review on the involvement of Nrf2/ARE signaling pathway

Natural compounds against doxorubicin‐induced cardiotoxicity: A review on the involvement of Nrf2/ARE signaling pathway

CYP1B1 as a therapeutic target in cardio-oncology

Orosomucoid 1 Attenuates Doxorubicin-Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

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