Regulated cell death pathways in doxorubicin-induced cardiotoxicity

Cell Death and Disease, Год журнала: 2021, Номер 12(4)

Опубликована: Апрель 1, 2021

Abstract Doxorubicin is a chemotherapeutic drug used for the treatment of various malignancies; however, patients can experience cardiotoxic effects and this has limited use potent drug. The mechanisms by which doxorubicin kills cardiomyocytes been elusive despite extensive research exact remain unknown. This review focuses on recent advances in our understanding induced regulated cardiomyocyte death pathways including autophagy, ferroptosis, necroptosis, pyroptosis apoptosis. Understanding leads to may help identify novel therapeutic agents lead more targeted approaches cardiotoxicity testing.

Язык: Английский

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New insights into the activities and toxicities of the old anticancer drug doxorubicin

FEBS Journal, Год журнала: 2020, Номер 288(21), С. 6095 - 6111

Опубликована: Окт. 6, 2020

The anthracycline drug doxorubicin is among the most used—and useful—chemotherapeutics. While highly effective in treatment of various hematopoietic malignancies and solid tumours, its application limited by severe adverse effects, including irreversible cardiotoxicity, therapy‐related gonadotoxicity. This continues to motivate investigation into mechanisms activities toxicities, with aim overcome latter without sacrificing former. It has long been appreciated that causes DNA double‐strand breaks due poisoning topoisomerase II. More recently, it became clear also leads chromatin damage achieved through eviction histones from select sites genome. Evaluation these analogues revealed makes a major contribution efficacy drugs. Furthermore, DNA‐damaging effect conspires cause number effects. Structure–activity relationships within family offer opportunities for chemical separation towards development In this review, we elaborate on our current understanding different their contributions side We then perspective how old anticancer can be amended new ways benefit cancer patients, providing improved quality life.

Язык: Английский

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Advances in understanding the role of P-gp in doxorubicin resistance: Molecular pathways, therapeutic strategies, and prospects

Drug Discovery Today, Год журнала: 2021, Номер 27(2), С. 436 - 455

Опубликована: Окт. 7, 2021

P-glycoprotein (P-gp) is a drug efflux transporter that triggers doxorubicin (DOX) resistance. In this review, we highlight the molecular avenues regulating P-gp, such as Nrf2, HIF-1α, miRNAs, and long noncoding (lnc)RNAs, to reveal their participation in DOX These antitumor compounds genetic tools synergistically reduce P-gp expression. Furthermore, ATP depletion impairs activity enhance of DOX. Nanoarchitectures, including liposomes, micelles, polymeric nanoparticles (NPs), solid lipid nanocarriers, have been developed for co-delivery with anticancer genes enhancing cytotoxicity. Surface modification instance hyaluronic acid (HA), can promote selectivity toward cancer cells. We discuss these aspects focus on expression activity.

Язык: Английский

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Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Oxidative Medicine and Cellular Longevity, Год журнала: 2021, Номер 2021(1)

Опубликована: Янв. 1, 2021

Ferroptosis is a nonapoptotic form of cell death characterized by iron‐dependent accumulation lipid hydroperoxides to lethal levels. Necroptosis, an alternative programmed necrosis, regulated receptor‐interacting protein (RIP) 1 activation and RIP3 mixed‐lineage kinase domain‐like (MLKL) phosphorylation. necroptosis both play important roles in the pathological progress ischemic stroke, which complex brain disease several pathways. In past few years, increasing evidence has suggested that crosstalk occurs between ferroptosis stroke. However, potential links stroke have not been elucidated yet. Hence, this review, we overview analyze mechanism underlying And find iron overload, one ferroptosis, leads mitochondrial permeability transition pore (MPTP) opening, aggravates RIP1 phosphorylation contributes necroptosis. addition, heat shock 90 (HSP90) induces promoting suppressing glutathione peroxidase 4 (GPX4) activation. work, try deliver new perspective exploration novel therapeutic targets for treatment

Язык: Английский

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Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Март 14, 2023

Doxorubicin (DOX) is a powerful and commonly used chemotherapeutic drug, alone or in combination variety of cancers, while it has been found to cause serious cardiac side effects clinical application. More more researchers are trying explore the molecular mechanisms DOX-induced cardiomyopathy (DIC), which oxidative stress inflammation considered play significant role. This review summarizes signaling pathways related DIC compounds that exert cardioprotective by acting on relevant pathways, including role Nrf2/Keap1/ARE, Sirt1/p66Shc, Sirt1/PPAR/PGC-1α NOS, NOX, Fe2+ stress, as well NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-κB, mTOR/TFEB/NF-κB inflammation. Hence, we attempt explain terms inflammation, provide theoretical basis new idea for further drug research reducing DIC. Video Abstract.

Язык: Английский

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Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Июнь 3, 2020

Homeostatic regulation of cardiomyocytes plays a crucial role in maintaining the normal physiological activity cardiac tissue. Severe cardiotoxicity results diseases including but not limited to arrhythmia, myocardial infarction and hypertrophy. Drug-induced limits or forbids further use implicated drugs. Such drugs that are currently available clinic include anti-tumor (doxorubicin, cisplatin, trastuzumab, etc.), antidiabetic (rosiglitazone pioglitazone), an antiviral drug (zidovudine). This review focused on cardiomyocyte death forms related mechanisms underlying clinical drug-induced cardiotoxicity, apoptosis, autophagy, necrosis, necroptosis, pryoptosis, ferroptosis. The key proteins involved signaling were discussed evaluated, aiming provide theoretical basis target for prevention treatment practice.

Язык: Английский

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Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Pharmaceutics, Год журнала: 2020, Номер 12(11), С. 1084 - 1084

Опубликована: Ноя. 11, 2020

Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cells are able obtain chemoresistance that limits DOX efficacy. In respect dose-dependent side effect DOX, enhancing its dosage not recommended for effective chemotherapy. Therefore, different strategies have been considered reversing resistance diminishing effects. Phytochemical potential candidates this case due their great pharmacological activities. Curcumin antitumor phytochemical isolated from Curcuma longa with capacity suppressing metastasis proliferation affecting molecular pathways. Experiments demonstrated curcumin inhibiting by downregulating oncogene pathways MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB AP-1. Furthermore, coadministration potentiates apoptosis induction cells. light this, nanoplatforms employed codelivery DOX. This results promoting bioavailability internalization aforementioned active compounds and, consequently, activity. Noteworthy, has reducing adverse effects on normal tissues via inflammation, oxidative stress apoptosis. The current review highlights anticancer mechanism, nanovehicles.

Язык: Английский

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Progress in Understanding Ferroptosis and Challenges in Its Targeting for Therapeutic Benefit

Cell chemical biology, Год журнала: 2020, Номер 27(4), С. 463 - 471

Опубликована: Апрель 1, 2020

Язык: Английский

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Research progress of therapeutic drugs for doxorubicin-induced cardiomyopathy

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 156, С. 113903 - 113903

Опубликована: Окт. 22, 2022

Doxorubicin (DOX), as a kind of chemotherapy agent with remarkable therapeutic effect, can be used to treat diverse malignant tumors clinically. Dose-dependent cardiotoxicity is the most serious adverse reaction after DOX treatment, which eventually leads cardiomyopathy and greatly limits clinical application DOX. DOX-induced not result single mechanistic action, multiple mechanisms have been discovered demonstrated experimentally, such oxidative stress, inflammation, mitochondrial damage, calcium homeostasis disorder, ferroptosis, autophagy apoptosis. Dexrazoxane (DEX) only protective approved by FDA for treatment cardiomyopathy, but its still has some limitations. Therefore, we need find other effective drugs soon possible. In this paper, that effectively improve in recent years are mainly described from aspects natural drugs, endogenous substances, new dosage forms, herbal medicines, chemical modification marketed drugs. The aim present study evaluate effects these on anticancer curative effects, so provide reference value future.

Язык: Английский

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atg7 -Based Autophagy Activation Reverses Doxorubicin-Induced Cardiotoxicity

Circulation Research, Год журнала: 2021, Номер 129(8)

Опубликована: Авг. 13, 2021

[Figure: see text].

Язык: Английский

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