Comparison of deferasirox and deferoxamine effects on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I

doi:10.4103/0973-6247.200768

Cited by 16 publications

(17 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results suggest that the mechanism of tumor immune microenvironment underlying iron deficiency may differ in various breast cancer cell lines. Moreover, according to deferasirox, another iron chelator, some previous studies revealed that deferasirox was noninferior or more effective than DFO regarding the iron removal [31,32]. In present study, though deferasirox showed inhibition of breast cancer proliferation and induction of hypoxia like DFO, it did not show the similar result with respect to EMT or immune check points.…”

Section: Discussioncontrasting

confidence: 64%

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

et al. 2020

View full text Add to dashboard Cite

Background Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. Methods Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. Results Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. Conclusions Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

show abstract

Section: Discussioncontrasting

confidence: 64%

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

et al. 2020

View full text Add to dashboard Cite

show abstract

“…These results suggest that the mechanism of tumor immune microenvironment underlying iron de ciency may differ in various breast cancer cell lines. Moreover, according to deferasirox, another iron chelator, some previous studies revealed that deferasirox was noninferior or more effective than DFO regarding the iron removal [31,32]. In present study, though deferasirox showed inhibition of breast cancer proliferation and induction of hypoxia like DFO, it did not show the similar result with respect to EMT or immune check points.…”

Section: Discussioncontrasting

confidence: 64%

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

Goto

Kashiwagi

Asano

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo.Methods: Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined.Results: Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone.Conclusions: Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

show abstract

“…A study by Al-Kuraishy and Al-Gareeb showed that serum ferritin levels, serum iron levels, and total iron-binding capacity in deferoxamine-treated patients were higher than those in deferasirox-treated patients; this was similar to our result. It seems that a high period of deferoxamine consumption can affect iron status in a patient during 12 months of treatment [34]. However, data from a meta-analysis suggest that a similar efficacy can be achieved depending on the ratio of doses of deferoxamine and deferasirox being compared [13].…”

Section: Discussionmentioning

confidence: 99%

Early Kidney Damage Markers after Deferasirox Treatment in Patients with Thalassemia Major: A Case-Control Study

Badeli

Baghersalimi

Eslami

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background. The life of patients with β-thalassemia major depends on blood transfusion. Regular blood transfusion leads to hemosiderosis in their main organs. The aim of this study was to compare the effects of deferasirox and deferoxamine on renal damage in patients with β-thalassemia major. Method. The present case-control study was conducted on 60 individuals who were referred to the 17th Shahrivar Tertiary Referral Hospital in Guilan province, Iran. In this study, patients with β-thalassemia major who used deferasirox (n=21) and patients who used deferoxamine (n=19) were evaluated. The control group (n=20) was selected from healthy individuals. Serum creatinine (CREA), blood urea nitrogen (BUN), and Cystatin C were measured from blood samples. Furthermore, urinary (U.) neutrophil gelatinase-associated lipocalin (NGAL), albumin (Alb), interleukin- (IL-) 18, and Kidney Injury Molecule-1 (KIM-1) were measured by the ELISA method and normalized for U. creatinine (CREA). Results. U. NGAL, U. IL-18, and BUN biomarkers in the deferasirox group were significantly higher than those in the control group (p<0.001). U. NGAL/CREA and U. KIM-1/CREA ratios increased in both the deferoxamine and deferasirox groups compared to the control group (p<0.05). U. Alb was significantly higher in patients treated with deferoxamine than in healthy participants (p<0.05). Conclusion. The findings of this study indicate that after taking deferasirox, there was renal damage and an increase in inflammatory factors. Also, minor renal impairment was observed after deferoxamine administration, but it was not confirmed at the molecular level (U. NGAL and KIM-1). Therefore, it seems that patients who are taking these two drugs should be monitored carefully.

show abstract

Comparison of deferasirox and deferoxamine effects on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia

Cited by 16 publications

References 27 publications

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

Early Kidney Damage Markers after Deferasirox Treatment in Patients with Thalassemia Major: A Case-Control Study

Contact Info

Product

Resources

About