Doxorubicin and metformin

Doxorubicin (DOX) is a widely used antitumor agent; however, its clinical application is limited by dose-related organ damage. Because organic cation/carnitine transporters (OCTN1 and OCTN2), which are critical for DOX uptake, are highly expressed in hepatocytes, we aimed to elucidate the role of these transporters in hepatic DOX uptake. The results indicated that inhibitors and RNA interference both significantly reduced DOX accumulation in HepG2 and HepaRG cells, suggesting that OCTN1/2 contribute substantially to DOX uptake by hepatocytes...

Surgery is the primary method to treat malignant melanoma; however, the residual microtumors that cannot be resected completely often trigger tumor recurrence, causing tumor-related mortality following melanoma resection. Herein, we developed a feasible strategy based on the combinational chemoimmunotherapy by cross-linking carboxymethyl chitosan (CMCS)-originated polymetformin (PolyMetCMCS ) with cystamine to prepare stimuli-responsive nanogel (PMNG) owing to the disulfide bond in cystamine that can be cleaved by the massive glutathione (GSH) in tumor sites...

OBJECTIVE: To explore whether metformin reduces cardiotoxicity of doxorubicin through the AMPK pathway. METHODS: We analyzed the data of 123 patients with myeloid leukemia, non-Hodgkin's lymphoma, or breast cancer receiving doxorubicin for phased chemotherapy, including 43 patients receiving combined treatment with metformin (test group) and 80 without metformin treatment (control group). The changes in plasma levels of CK-MB, LDH, and BNP, left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS) of the patients were observed...

Despite the fact that chemoimmunotherapy has emerged as a key component in the era of cancer immunotherapy, it is challenged by the complex tumor microenvironment (TME) that is jam-packed with cellular and non-cellular immunosuppressive components. The aim of this study was to design a nanoparticulate system capable of sufficiently accumulating in the tumor and spleen to mediate local and systemic immune responses, respectively. The study also aimed to remodel the immunosuppressive TME. For such reasons, multi-functional polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) were engineered to simultaneously eradicate the cancer cells, silence the tumor-associated fibroblasts (TAFs), and re-educate the tumor-associated macrophages (TAMs) using doxorubicin, losartan, and metformin, respectively...

Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15...

Doxorubicin (DOX) has been widely used to treat various tumors; however, DOX-induced cardiotoxicity limits its utilization. Since high accumulation of DOX in cardiomyocytes/mitochondria is the key reason, we aimed to clarify the mechanisms of DOX uptake and explore whether selectively inhibiting DOX uptake transporters would attenuate DOX accumulation and cardiotoxicity. Our results demonstrated that OCTN1/OCTN2/PMAT (organic cation/carnitine transporter 1/2 or plasma membrane monoamine transporter), especially OCTN2, played crucial roles in DOX uptake in cardiomyocytes, while OCTN2 and OCTN1 contributed to DOX transmembrane transport in mitochondria...

INTRODUCTION: The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC...

Ferroptosis has been suggested to involve in doxorubicin (DOX)-induced cardiotoxicity. However, the underlying mechanisms and regulatory targets of cardiomyocyte ferroptosis remains to be understood. This study demonstrated that the up-regulation of ferroptosis associated proteins genes were accompanied with the down-regulation of AMPKα2 phosphorylation in DOX treated mouse heart or neonatal rat cardiomyocytes (NRCMs). AMPKα2 knockout (AMPKα2-/-) significantly exacerbated mouse cardiac dysfunction, increased mortality, promoting ferroptosis associated mitochondrial injuries, enhanced ferroptosis associated proteins and genes expression, and lead to accumulation of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in mouse serum and hearts respectively...

FOXO3a is an inevitable transcription factor, which is involved in the regulation of biological processes such as proliferation, DNA damage repair, cell cycle arrest and cell death. Previous studies confirmed that FOXO3a is an excellent tumor suppressor and in cancer cells, it gets phosphorylated followed by proteasomal degradation. FOXO3a is found to be inactivated in cancer cells, whereas in normal cells it gets activated and upregulates its downstream targets, which induces apoptotic pathways. Hence, activation of FOXO3a can be implicated in cancer prevention and treatment...

INTRODUCTION: Cervical cancer is a worldwide health problem due to the number of deaths caused by this neoplasm. In particular, in 2020, 30,000 deaths of this type of tumor were reported in Latin America. Treatments used to manage patients diagnosed in the early stages have excellent results as measured by different clinical outcomes. Existing first-line treatments are not enough to avoid cancer recurrence, progression, or metastasis in locally advanced and advanced stages. Therefore, there is a need to continue with the proposal of new therapies...

Introduction: Doxorubicin (DOX), a chemotherapeutic drug, induces senescence and increases the secretion of senescence-associated secretory phenotype (SASP) in endothelial cells (ECs), which contributes to DOX-induced inflammaging. Metformin, an anti-diabetic drug, demonstrates senomorphic effects on different models of senescence. However, the effects of metformin on DOX-induced endothelial senescence have not been reported before. Senescent ECs exhibit a hyper-inflammatory response to lipopolysachharide (LPS)...

The broad-spectrum antineoplastic drug doxorubicin (DOX) has one of the most serious chronic side effects on the heart, dilated cardiomyopathy, but the precise molecular mechanisms underlying disease progression subsequent to long latency periods remain puzzling. Here, we established a model of DOX-induced dilated cardiomyopathy. In a cardiac cytology exploration, we found that differentially expressed genes in the KEGG signaling pathway enrichment provided a novel complex network of mTOR bridging autophagy and oxidative stress...

Doxorubicin (DOX) is a frequent chemotherapeutic drug used to treat various malignant tumors. One of the key factors that diminish its therapeutic importance is DOX-induced nephrotoxicity. The first-line oral antidiabetic drug is metformin (Met), which also has antioxidant properties. The purpose of our study was to investigate the underlying molecular mechanisms for the potential protective effects of Met on DOX-triggered nephrotoxicity. Four animal groups were assigned as follows; animals received vehicle (control group), 200 mg/kg Met (Met group), DOX 15 mg/kg DOX (DOX group), and a combination of DOX and Met (DOX/Met group)...

OBJECTIVES: The present study aimed to evaluate the effect of metformin pretreatment on the potentiation of antiproliferative action of doxorubicin against breast cancer. MATERIAL AND METHODS: Female Wistar rats were administered with 7,12-Dimethylbenz(a)anthracene (DMBA) (35mg) in 1mL olive oil subcutaneously beneath the mammary gland. Animals were pretreated with metformin (Met) 200mg/kg two weeks before DMBA administration. DMBA control groups received doxorubicin (Dox) (4mg/kg and 2mg/kg), Met (200mg/kg) alone and in combination with Dox (4mg/kg)...

Pyroptosis is an inflammasome-induced lytic form of programmed cell death, and its main effect involves the release of inflammatory mediators when a cell dies, resulting in an inflammatory response in the body. The key to pyroptosis is the cleavage of GSDMD or other gasdermin families. Some drugs can cause cleavage GSDMD or other gasdermin members cause pyroptosis and suppress cancer growth and development. This review explores several drugs that may induce pyroptosis, thereby contributing to tumor treatment...

In the tumor microenvironment (TME), the extracellular matrix (ECM) produced by cancer-associated fibroblasts (CAFs) forms a dense barrier that prevents nanodrugs from penetrating into deep tumor sites, leading to unsatisfactory therapeutic effects. Recently, it has been found that ECM depletion and using small-sized nanoparticles are effective strategies. Herein, we reported a detachable dual-targeting nanoparticle (HA-DOX@GNPs-Met@HFn) based on reducing ECM for enhancing penetration. When these nanoparticles reached the tumor site, the nanoparticles were divided into two parts in response to matrix metalloproteinase-2 overexpressed in TME, causing a decrease in the nanoparticle size from about 124 to 36 nm...

Doxorubicin is a widely used anticancer drug whose efficacy is limited due to its cardiotoxicity. There is no ideal cardioprotection available against doxorubicin-induced cardiotoxicity. This study aimed to investigate the anticipated cardioprotective potential of metformin and dapagliflozin against doxorubicin-induced acute cardiotoxicity in Wistar rats. At the beginning of the experiment, cardiac screening of experimental animals was done by recording an electrocardiogram (ECG) before allocating them into the groups...

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AIMS: Oxidative stress and inflammation have been linked to doxorubicin (DOX)-induced cardiotoxicity, while the exact molecular processes are currently under investigation. The goal of this study is to investigate Metformin's preventive role in cardiotoxicity induced by DOX. MATERIALS AND METHODS: Male albino mice were divided randomly into four groups. Metformin (Met) 200 mg/kg orally (p.o.) was given either alone or when combined with a single DOX (15 mg/kg; i...

Hyperphosphatemia can occur as a result of reduced phosphate (Pi ) excretion in cases of kidney dysfunction, which can induce muscle wasting and suppress myogenic differentiation. Higher Pi suppresses myogenic differentiation and promotes muscle atrophy through canonical (oxidative stress-mediated) and noncanonical (p62-mediated) activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. However, the crosstalk between myogenin and Nrf2/p62 and potential drug(s) for the regulation of myogenin expression needed to be addressed...