Effect of Doxorubicin on Fibroblast Migration and Proliferation

Izaguirre, Lucía B.; Pinilla, Isabel; Gonzalvo, F; Pérez, Salud; Fm, Honrubia

doi:10.1385/ao:35:1:48

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…Doxorubicin is an anthracycline antibiotic that has been commonly used in the cancer treatment for more than 40 years [34, 47]. Doxorubicin is known to induce various severe side effects in clinical application including poor wound healing [48, 49]. In this study, we observed that doxorubicin inhibited cell migration, altered cell morphology, and reduced microtubule mass at high cytotoxic concentrations in U2OS cells, which could explain these clinical reports.…”

Section: Discussionsupporting

confidence: 52%

“…However, doxorubicin did not show impact on tubulin assembly in vitro (Additional file 1: Table S1), indicating that direct effects on microtubules are not involved in its mechanism. Doxorubicin impaired cell migration probably via the inhibition of protein synthesis and prolyl 4-hydroxylase [49]. Generally, doxorubicin could be referred as an anti-migrating agent but its clinical administration should be further studied and more research is needed to improve the therapeutic efficiency and decrease its side effects.…”

Section: Discussionmentioning

confidence: 99%

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In vitro wound healing of tumor cells: inhibition of cell migration by selected cytotoxic alkaloids

Wang

Decker

Zechner

et al. 2019

BMC Pharmacol Toxicol

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BackgroundCell migration is involved in several pathological processes such as tumor invasion, neoangiogenesis and metastasis. Microtubules are needed in directional migration.MethodsTo investigate the effects of microtubule-binding agents (paclitaxel, vinblastine, colchicine, podophyllotoxin), benzophenanthridine alkaloids (sanguinarine, chelerythrine, chelidonine) and other anti-tumor drugs (homoharringtonine, doxorubicin) on cell migration, we performed the in vitro wound healing assay. The interactions between selected alkaloids and microtubules were studied via U2OS cells expressing microtubule-GFP markers.ResultsThe microtubule-binding natural products paclitaxel, vinblastine, colchicine and podophyllotoxin significantly altered microtubule dynamics in living cells and inhibited cell migration at concentrations below apparent cytotoxicity. The benzophenanthridine alkaloid sanguinarine, chelerythrine and chelidonine which affected microtubules in living cells, did not inhibit cell migration. Homoharringtonine (protein biosynthesis inhibitor) and doxorubicin significantly inhibited cell migration, however, they did not exert obvious effects on microtubules.ConclusionIn this study, we demonstrated that microtubule-binding agents are effective anti-migrating agents; moreover, homoharringtonine and doxorubicin can be referred as anti-migrating agents, but direct microtubule dynamics are not involved in their mode of action. Our study provides evidence that some alkaloids and other microtubule-binding natural products may be interesting candidates for the development of novel agents against metastasis.Electronic supplementary materialThe online version of this article (10.1186/s40360-018-0284-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

In vitro wound healing of tumor cells: inhibition of cell migration by selected cytotoxic alkaloids

Wang

Decker

Zechner

et al. 2019

BMC Pharmacol Toxicol

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“…S15 ). Such a high cytotoxicity towards normal cell lines is typical for anticancer drug, e.g., doxorubicin inhibits fibroblasts migration and proliferation even at concentration 10 −6 M (0.5 µg/ml), whereas doses at 5·10 −5 M and higher showed cellular toxicity and effectively inhibits wound repair 47 – 49 . Though the study on 3D fibroblast culture may give different result, the only local application of hyaluronic acid/MAg NPs gel may be considered.…”

Section: Resultsmentioning

confidence: 99%

Gel with silver and ultrasmall iron oxide nanoparticles produced with Amanita muscaria extract: physicochemical characterization, microstructure analysis and anticancer properties

Ivashchenko

Przysiecka

Peplińska

et al. 2018

Sci Rep

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Combination therapy remains one of the most promising and intensively developed direction in cancer treatment. This study is aimed to combine and investigate the anticancer properties of silver nanoparticles (NPs) and Amanita muscaria mushroom in gel formulation. For this, hyaluronic acid was used as gel-forming agent, whereas Amanita muscaria extract was used as capping agent during silver and ultrasmall iron oxide (MAg) NPs synthesis. Amanita muscaria compounds formed NP’s surface layer and contributed anticancer properties, whereas silver NPs contributed anticancer, fluorescence and photoactive properties to the gel. Physicochemical characterization included X-ray diffraction (XRD), microscopies (SEM, cryo-SEM, TEM, confocal fluorescence), spectrofluorometric method, thermogravimetric analysis (TGA), dynamic light scattering (DLS) techniques, energy dispersive (EDS), Fourier transform infrared (FTIR) and ultraviolet–visible (UV-Vis) spectroscopies, zeta-potential and rheological measurements. Microstructure analysis of hyaluronic acid/MAg NPs gel was performed by cryo-SEM technique. We showed that hyaluronic acid is a perfect gel-forming agent from both biomedical and technological points of view. It is well-mixed with MAg NPs forming stable gel formulation; high homogeneity of hyaluronic acid/MAg NPs gel was shown by SEM EDS elemental mapping. Microstructure of the gel was found to be highly ordered and consisted of domains from perforated parallel tubular structures. This finding expanded our understanding of gels and broke the stereotype of gel structure as chaotic network of fibers. Cytotoxicity studies performed on 2D and 3D HeLa cell cultures pointed to a high potential of hyaluronic acid/MAg NPs gel for local treatment of cancer. Cell response was found to be significantly different for 2D and 3D cell cultures that was related to their different cytoarhitecture and gene expression. Thus, the results of the cellular spheroids viability showed that they were significantly more resistant to the cytotoxic action of MAg NPs and their gel formulation than 2D cell culture. Hyaluronic acid used as gelling agent in gel formulation was found to increase an effectiveness of active components (MAg NPs, Amanita muscaria extract) probably improving their transport inside HeLa spheroids.

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Doxorubicin‐Induced Cardiomyopathy in Children

Mancilla

Iskra

Aune

2019

Comprehensive Physiology

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Doxorubicin-induced cardiotoxicity in childhood cancer survivors is a growing problem. The population of patients at risk for cardiovascular disease is steadily increasing, as five-year survival rates for all types of childhood cancers continue to improve. Doxorubicin affects the developing heart differently from the adult heart and in a subset of exposed patients, childhood exposure leads to late, irreversible cardiomyopathy. Notably, the prevalence of late-onset toxicity is increasing in parallel with improved survival. By the year 2020, it is estimated that there will be 500,000 childhood cancer survivors and over 50,000 of them will suffer from doxorubicin-induced cardiotoxicity. The majority of the research to-date, concentrated on childhood cancer survivors, has focused mostly on clinical outcomes through well-designed epidemiological and retrospective cohort studies. Preclinical studies have elucidated many of the cellular mechanisms that elicit acute toxicity in cardiomyocytes. However, more research is needed in the areas of early-and late-onset cardiotoxicity and more importantly improving the scientific understanding of how other cells present in the cardiac milieu are impacted by doxorubicin exposure. The overall goal of this review is to succinctly summarize the major clinical and preclinical studies focused on doxorubicin-induced cardiotoxicity. As the prevalence of patients affected by doxorubicin exposure continues to increase, it is imperative that the major gaps in existing research are identified and subsequently utilized to develop appropriate research priorities for the coming years. Well-designed preclinical research models will enhance our understanding of the pathophysiology of doxorubicin-induced cardiotoxicity and directly lead to better diagnosis, treatment, and prevention.

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Effect of Doxorubicin on Fibroblast Migration and Proliferation

Cited by 7 publications

References 36 publications

In vitro wound healing of tumor cells: inhibition of cell migration by selected cytotoxic alkaloids

In vitro wound healing of tumor cells: inhibition of cell migration by selected cytotoxic alkaloids

Gel with silver and ultrasmall iron oxide nanoparticles produced with Amanita muscaria extract: physicochemical characterization, microstructure analysis and anticancer properties

Doxorubicin‐Induced Cardiomyopathy in Children

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