Molecular mechanisms of endothelial remodeling under doxorubicin treatment

Podyacheva, Ekaterina; Danilchuk, Maria; Toropova, Yana

doi:10.1016/j.biopha.2023.114576

Cited by 13 publications

(4 citation statements)

References 185 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this process, ECs lose their adhesive properties and gain migratory and invasive characteristics with increased vascular permeability. EndoMT is a part of the molecular mechanisms of endothelial remodelling under Dox treatment [ 14 ]. In preliminary protein analysis, we could observe increased expression of mesenchymal markers in HMEC-1 upon combined treatment.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin

Bernardo

Klein

Heinzelmann

et al. 2023

IJMS

View full text Add to dashboard Cite

Surgery, radiotherapy, and chemotherapy are essential treatment modalities to target cancer cells, but they frequently cause damage to the normal tissue, potentially leading to side effects. As proton beam radiotherapy (PBT) can precisely spare normal tissue, this therapeutic option is of increasing importance regarding (neo-)adjuvant and definitive anti-cancer therapies. Akin to photon-based radiotherapy, PBT is often combined with systemic treatment, such as doxorubicin (Dox). This study compares the cellular response of human microvascular endothelial cells (HMEC-1) following irradiation with photons (X) or protons (H) alone and also in combination with different sequences of Dox. The cellular survival, cell cycle, apoptosis, proliferation, viability, morphology, and migration were all investigated. Dox monotreatment had minor effects on all endpoints. Both radiation qualities alone and in combination with longer Dox schedules significantly reduced clonogenic survival and proliferation, increased the apoptotic cell fraction, induced a longer G2/M cell cycle arrest, and altered the cell morphology towards endothelial-to-mesenchymal-transition (EndoMT) processes. Radiation quality effects were seen for metabolic viability, proliferation, and motility of HMEC-1 cells. Additive effects were found for longer Dox schedules. Overall, similar effects were found for H/H-Dox and X/X-Dox. Significant alterations between the radiation qualities indicate different but not worse endothelial cell damage by H/H-Dox.

show abstract

Section: Discussionmentioning

confidence: 99%

“…EndoMT is a biological process in which ECs lose their characteristic phenotype and transform into mesenchymal cells with a fibroblast-like appearance. Moreover, the endothelial damage in DIC leads to the disruption of the endothelial barrier function and increases vascular permeability, resulting in inflammation [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin

Bernardo

Klein

Heinzelmann

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Further and more specific studies are indeed required to fully establish if FAM46C expression is synergistic or not with the anti-cancer activities of either lenalidomide or pomalidomide. Doxorubicin is an anthracyline drug usually used in combination with bortezomib for MM treatment but also utilized to treat leukaemias, non-Hodgkin lymphomas and a broad range of other cancers [90], while melphalan is an alkylating agent used for general treatment of haematological malignancies.…”

Section: Lenalidomide and Pomalidomidementioning

confidence: 99%

Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance

Lai,

De Grossi,

Catusi

et al. 2024

Cancers

View full text Add to dashboard Cite

FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin.

show abstract

“…Dysfunction of the vascular endothelial barrier in cancer has been implicated in disease pathology, progression, and outcome [ 6 , 130 ], as vascular endothelial cells have a key role during tumor metastasis [ 131 ], and the interaction between cancer cell and endothelium has been documented in research models for migration through the blood–brain barrier [ 132 ]. In particular, endothelial–mesenchymal transition has been proposed to occur after anthracycline treatment and to initiate vascular remodeling [ 133 ]; anthracyclines are known triggers of NFκB activation [ 134 ] and specifically initiate endothelial-to-mesenchymal transition [ 135 ] on the one hand, and on the other hand, NFκB activation protects cancer cells from apoptosis [ 136 ].…”

Section: Phenotypic Transitions In the Microenvironmentmentioning

confidence: 99%

OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer

Vlahopoulos,

Pan,

Varisli

et al. 2023

Cancers

View full text Add to dashboard Cite

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now also recognized as a modulator of gene expression. What is important for cancer is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, such as NFκB to their cognate sites, enabling the expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which hold significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. This review analyzes and discusses how these cells adapt through redox-modulated intricate connections, via interaction of OGG1 with NFκB, which provides malignant cells with alternative molecular pathways to transform their microenvironment, enabling adjustment, promoting cell proliferation, metastasis, and evading killing by therapeutic agents.

show abstract

Molecular mechanisms of endothelial remodeling under doxorubicin treatment

Cited by 13 publications

References 185 publications

Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin

Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin

Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance

OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer

Contact Info

Product

Resources

About