scholarly journals Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation

2021 ◽  
Vol 22 (8) ◽  
pp. 4153
Author(s):  
Kutlwano R. Xulu ◽  
Tanya N. Augustine
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Antiplatelet Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.

The α2δ1 subunit of the voltage-gated calcium channel as a potential candidate for breast cancer tumor initial cells biomarker

2021 ◽  
pp. 1-11
Author(s):  
Meng Li ◽  
Wenmin Zhang ◽  
Xiaodan Yang ◽  
Guo An ◽  
Wei Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Self Renewal

BACKGROUND: The voltage-gated calcium channel subunit alpha 2 delta 1 (α2δ1) is a functional tumor initial cells (TICs) marker for some solid cancer cells. This study aimed to investigate whether α2δ1 can be used as a potential TIC marker for breast cancer cells. METHODS: α2δ1+ and α2δ1- cells were identified and sorted from the breast cancer cell lines MDA-MB-231, MDA-MB-435s and ZR-75-1 by Immunofluorescence (IF) and Fluorescent-activated cell sorting (FACS) analyses. Spheroid formation in vitro and tumorigenesis in NOD/SCID mice were assessed to determine the self-renewal and serial transplantation abilities of these cells. Using a lentivirus infection system for α2δ1 in breast cancer cell lines, we determined the mRNA levels of stemnessassociated genes by quality real-time PCR (qRT-PCR). Boyden chamber and wounding assays were further performed to detect the migration of α2δ1 overexpression cells. Bioinformatics explored the relationship of molecular classification of breast cancer and drug resistance. RESULTS: α2δ1 presents on the cytomembrane of breast cancer cells, with a positive rate of 1.5–3%. The α2δ1+ cells in breast cancer cell lines have a stronger self-renewal ability and tumor initiating properties in vitro and in vivo. Overexpressing α2δ1 successfully enhanced the sphere-forming efficiency, and upregulated the expression of stemness-associated genes, and increased cell migration. However, seldom significant was available between estrogen receptor +/- (ER+/-), progesterone receptor (PR+/-), and Her2+/-. CONCLUSIONS: Breast cancer cells positive for the α2δ1 charactered tumor initiation, and α2δ1 is a potential TIC marker for breast cancer that further promotes the migration.

Solanum nigrum Anticancer Effect Through Epigenetic Modulations in Breast Cancer Cell Lines

2020 ◽  
Vol 16 (2) ◽  
pp. 121-126
Author(s):  
Atefeh Shirkavand ◽  
Zahra N. Boroujeni ◽  
Seyed A. Aleyasin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Methylation Status ◽  
Cancer Cell Lines ◽  
Solanum Nigrum ◽  
Breast Cancer Cell Lines

Background: DNA methylation plays an important role in the regulation of gene expression in mammalian cells and often occurs at CpG islands in the genome. It is more reversible than genetic variations and has therefore attracted much attention for the treatment of many diseases, especially cancer. In the present study, we investigated the effect of Solanum nigrum Extract (SNE) on the methylation status of the VIM and CXCR4 genes in breast cancer cell lines. Methods: The Trypan blue assay was used to study the effect of SNE at various concentrations of 0, 0.1, 1.5, 2.5, 3.5 and 5 mg/ml for 48 h on the survival of three human breast cancer cell lines MCF7, MDA-MB-468, MDA-MB-231. Methylation status of VIM and CXCR4 genes in breast cancer cell lines was assessed by Methylation-Specific PCR (MSP) method. Also, methylation changes of VIM and CXCR4 genes in breast cancer cell lines after treatment with 0.1 mg/ml of SNE for 6 days were analyzed by MSP method. To confirm the effect of SNE on methylation of VIM and CXCR4 genes, Real-Time PCR was performed. Results: The Trypan blue assay results indicated that treatment with SNE reduced cell viability in a dose-dependent manner in breast cancer cells. Our results showed that treatment of breast cancer cells with 0.1 mg/ml of SNE hypermethylated the VIM, CXCR4 genes and significantly reduced the expression levels of their mRNA (P<0.05). Conclusion: Our findings reveal for the first time the impact of SNE on the methylation of breast cancer cells.

scholarly journals Studying the Genomic Role of Cathepsin-D in ER+ Breast Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A817-A818
Author(s):  
Elham Dianati ◽  
Emmanuelle Liaudet-coopman ◽  
Sylvie Mader
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cathepsin D ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Proximity Ligation Assay ◽  
Breast Cancer Cell Lines

Abstract Estrogen receptor alpha (ERα), a transcription factor implicated in induction of cell growth in breast cancer, is a therapeutic target that is expressed in &gt;70% of breast tumors. The transcriptional activity of ERα is controlled by ligands and increased through its interaction with co-activators such as the p160/SRC and p300/CBP families. In an attempt to identify the ligand-specific protein complexes involved in transcriptional regulation by ERα, BioID and TurboID screens were performed in two ER+ breast cancer cell lines, T-47D and ZR-75-1. Surprisingly, Cathepsin-D (Cath-D), a lysosomal aspartyl endoproteinase that is an ER target gene, was identified in these screens. Cath-D expression is associated with a poor prognosis and increased metastasis rate in breast cancer irrespective of its catalytic activities {Glondu, 2001 #119}[i]. Cath-D is localized in part to the nucleus where it interacts with TRPS1, a repressor of GATA-mediated transcription and modulator of ERα signaling {Bach, 2015 #117}[ii]. Co-silencing Cath-D and TRPS1 suppressed cell proliferation and inhibited growth under soft agar, suggesting that they cooperate to drive tumorigenesis {Bach, 2015 #117}[ii]. We hypothesized that Cath-D plays genomic as well as non-genomic roles in breast tumor aggressiveness and may alter ERα-mediated transcription. The nuclear localization of Cath-D was confirmed by immunofluorescence using different commercialized antibodies and observed in western blots of chromatin-bound fractions in three different ERα+ breast cancer cell lines, T-47D, ZR-75 and MCF-7. Specificity of the antibodies was confirmed using siRNA-mediated suppression of Cath-D. Moreover, Cath-D was also identified in proximity to TurboID-ERα by LC-MS after chromatin fractionation. The proximity of ERα and Cath-D both in the cytoplasm and nucleus was confirmed by proximity Ligation Assay (PLA) in three ER+ cell lines. Co-immunoprecipitation assays indicated physical interaction of Cath-D with ERα in T-47D cell extracts. Further, Cath-D was detected by ChIP-qPCR on estrogen response elements (EREs) of two ERα target genes, TFF1 and GREB1 in T-47D and ZR-75 cells. These results suggest that Cath-D can interact with ERα on DNA and play genomic roles in ER+ breast cancer cells. [i] Glondu, M., et al. (2001). “A mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells.” Oncogene20(47): 6920-6929. [ii] Bach, A. S., et al. (2015). “Nuclear cathepsin D enhances TRPS1 transcriptional repressor function to regulate cell cycle progression and transformation in human breast cancer cells.” Oncotarget6(29): 28084-28103.

Synthesis and Bio-evaluation of 2-Alkyl Substituted Fluorinated Genistein Analogues Against Breast Cancer

2021 ◽  
Vol 17 ◽  
Author(s):  
Yingl Zhu ◽  
Fan Zheng ◽  
Can Xiao ◽  
Xiaohe Liu ◽  
Xu Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Inhibitory Effects

Background: Breast cancer is the leading cause of cancer death in women. The current methods of chemotherapy for breast cancer generally have strong adverse reactions and drug resistance. Therefore, the discovery of novel anti-breast cancer lead compounds is urgently needed. Objective: Design and synthesize a series of 2-alkyl substituted fluorinated genistein analogues and evaluate their anti-breast cancer activity. Methods: Target compounds were obtained in a multistep reaction synthesis. The anti-tumor activity of compounds I-1~I-35 were evaluated with MCF-7, MDA-MB-231, MDA-MB-435, and MCF-10A cell lines in vitro, with tamoxifen as the positive control. Molecular docking was used to study the interaction between the synthesized compounds and PI3K-gamma. Results: A series of 2-alkyl substituted fluorinated genistein analogues were designed, synthesized and screened for their bioactivity. Most of the compounds displayed better selectivity toward breast cancer cell lines as compared with tamoxifen. Among these analogues, I-2, I-3, I-4, I-9, I-15 and I-17 have the strongest selective inhibition of breast cancer cells. Compounds I-10, I-13, I-15, I-17 and I-33 were found to have significant inhibitory effects on breast cancer cells. Molecular docking studies have shown that these compounds may act as PI3Kγ inhibitors and may further exhibit anti-breast cancer effects. Conclusion: Most of the newly synthesized compounds could highly selectively inhibit breast cancer cell lines. The experimental results indicate that the synthesized analogs may also have obvious selective inhibitory effects on other malignant proliferation cancer cells.

scholarly journals A systematic flux analysis approach to identify metabolic vulnerabilities in human breast cancer cell lines

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Sheree D. Martin ◽  
Sean L. McGee
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Flux Analysis ◽  
Human Breast

Abstract Background Increased flux through both glycolytic and oxidative metabolic pathways is a hallmark of breast cancer cells and is critical for their growth and survival. As such, targeting this metabolic reprograming has received much attention as a potential treatment approach. However, the heterogeneity of breast cancer cell metabolism, even within classifications, suggests a necessity for an individualised approach to treatment in breast cancer patients. Methods The metabolic phenotypes of a diverse panel of human breast cancer cell lines representing the major breast cancer classifications were assessed using real-time metabolic flux analysis. Flux linked to ATP production, pathway reserve capacities and specific macromolecule oxidation rates were quantified. Suspected metabolic vulnerabilities were targeted with specific pathway inhibitors, and relative cell viability was assessed using the crystal violet assay. Measures of AMPK and mTORC1 activity were analysed through immunoblotting. Results Breast cancer cells displayed heterogeneous energy requirements and utilisation of non-oxidative and oxidative energy-producing pathways. Quantification of basal glycolytic and oxidative reserve capacities identified cell lines that were highly dependent on individual pathways, while assessment of substrate oxidation relative to total oxidative capacity revealed cell lines that were highly dependent on individual macromolecules. Based on these findings, mild mitochondrial inhibition in ESH-172 cells, including with the anti-diabetic drug metformin, and mild glycolytic inhibition in Hs578T cells reduced relative viability, which did not occur in non-transformed MCF10a cells. The effects on viability were associated with AMPK activation and inhibition of mTORC1 signalling. Hs578T were also found to be highly dependent on glutamine oxidation and inhibition of this process also impacted viability. Conclusions Together, these data highlight that systematic flux analysis in breast cancer cells can identify targetable metabolic vulnerabilities, despite heterogeneity in metabolic profiles between individual cancer cell lines.

scholarly journals WD-3 inhibits the proliferation of breast cancer cells by regulating the glycolytic pathway

2020 ◽  
Author(s):  
Xiaodan Zhu ◽  
Lu Zhao ◽  
Jianliang You ◽  
Yiqun Ni ◽  
Zhipeng Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Hexokinase 2 ◽  
Mcf 7

Number 3 Prescription (WD-3) is an herbal remedy used in traditional Chinese medicine that has been shown to improve the outcomes of patients with advanced colon and gastric cancers. This study aimed to investigate the effect of WD-3 on proliferation, glycolysis, and hexokinase 2 expression in breast cancer cells. Four breast cancer cell lines (MDA-MB-231, BT-549, MCF-7, and MCF-7/ADR-RES) were treated with different concentrations of WD-3 compared with blank control (phosphate-buffered saline). Each of the breast cancer cell lines was also divided into WD-3, paclitaxel, and blank control group. Cell proliferation and morphology were assessed by MTT assay, nuclear Hoechst 33258 staining, or immunofluorescence. Apoptosis was analyzed by flow cytometry. High performance liquid chromatography was used for measurement of ATP, ADP, and AMP. Hexokinase 2 expression was analyzed by Western blot and quantitative reverse transcription PCR. WD-3 inhibited proliferation and increased apoptosis in all four breast cancer cell lines, in a dose-dependent manner. ATP and EC (energy charge) were significantly decreased in WD-3-treated BT-549 and MDA-MB-231 cells. WD-3 significantly downregulated the protein and mRNA expression of hexokinase II in BT-549 cells, however, not in the other three breast cancer cell lines. Our findings indicate that WD-3 targets the glycolytic pathway in breast cancer cells to exert its antitumor activity.

Soluble Inflammatory Mediators Proteinase-3 and Neutrophil Elastase Are Targeted by PR1-Specific Immunotherapy After Cellular Uptake and Cross Presentation of PR1 Peptide by Breast Cancer Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2089-2089
Author(s):  
Gheath Alatrash ◽  
Elizabeth Mittendorf ◽  
Anna Sergeeva ◽  
Pariya Sukhumalchandra ◽  
Na Qiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cross Presentation ◽  
Mcf 7

Abstract Abstract 2089 The human leukocyte antigen (HLA)-A2 restricted nonapeptide PR1 (VLQELNVTV) was shown to be immunogenic in leukemia. A phase I/II clinical trial has been initiated with PR1 peptide vaccine and to date has demonstrated clinical efficacy, including complete remission and immunologic responses in patients with acute (AML) and chronic (CML) myeloid leukemia, as well as myelodysplastic syndrome. PR1 is derived from the serine proteases proteinase-3 (P3) and neutrophil elastase (NE), which are normally found within neutrophil azurophil granules and are released into the inflammatory milieu. We have shown that P3 and NE are taken up and cross presented by antigen presenting cells and that their cross presentation elicits PR1 immunity. Because P3 and NE are present in breast cancer biopsies, we hypothesized that P3/NE may be taken up by breast cancer cells and cross presented to PR1-CTL. We recently demonstrated that the breast cancer cell lines MDA-MB-231, MDA-MB-453, MCF-7 and HER18 do not endogenously express NE and that NE is taken up by these cell lines. In this report, using PCR, western blot and flow cytometry, we show that P3 also is NOT endogenously expressed by the breast cancer cell lines MDA-MB-231, MDA-MB-453, MCF-7 or HER18. Using confocal microscopy, we demonstrate that P3 is taken up by these breast cancer cell lines within 10 minutes of pulsing and localizes to LAMP-2 containing lysosomal vesicles by 4 hours, suggesting its processing for presentation by (HLA)-I (i.e. HLA-A2). Using 8F4, the novel PR1-HLA-A2 monoclonal antibody, we show that PR1 is cross presented from P3 by 3 of 4 HLA-A2+ breast cancer cell lines (MDA-MB-231, MDA-MB-453-A2+, MCF-7), and from NE by 1 of 4 breast cancer cell lines (MDA-MB-231). Next, we studied whether PR1 presentation made cells susceptible to PR1-specific killing by PR1-CTL and the 8F4 monoclonal antibody. We show that following 12-hour pulsing of the MDA-MB-231 cell line with NE or P3, PR1 CTLs killed up to 31% and 38% of the NE- or P3-pulsed breast cancer cells respectively, vs. <1% of ovalbumin (ova)-pulsed MDA-MB-231cells. Additionally, in a complement mediated cytotoxicity assay using 8F4 antibody, pulsing of MDA-MB-231 cells with P3 led to 60% cytotoxicity (vs. 40% in ova-pulsed cells). In conclusion, this study shows that 1) PR1 is cross presented by breast cancer cells following uptake of soluble P3 and NE and 2) PR1 expression makes breast cancer a target of PR1-specific immunotherapy. If uptake of P3 or NE, present in the inflammatory milieu of other solid tumors, also leads to PR1 cross presentation, then PR1-based immunotherapy may be useful to treat other non-hematopoietic tumors. These results support a new paradigm linking inflammation and innate immunity to adaptive immune responses to cancer. Disclosures: No relevant conflicts of interest to declare.

Effect of enzastaurin on cell signaling, proliferation and apoptosis in breast cancer cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14121-14121
Author(s):  
B. Spankuch ◽  
E. Kurunci-Csacsko ◽  
T. Bauknecht ◽  
K. Strebhardt
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Caspase 9

14121 Background: Enzastaurin, an acyclic bisindolylmaleimide, is a potent selective serine/threonine kinase inhibitor that inhibits PKCβ, targets the PI3K/AKT pathway, and inhibits GSK3β phosphorylation. Enzastaurin induced apoptosis and decreased proliferation of various cancer lines, and decreased VEGF expression and microvessel density in human tumor xenografts. In animal models, enzastaurin had antitumor/antiangiogenic activity in non-small-cell lung, colon, renal cell, hepatocellular, and other cancers. Therefore, we sought to determine enzastaurin’s impact on cellular PKCβ-mediated signaling in breast cancer cells. Secondarily, we sought to determine the induction of the apoptotic cascade by enzastaurin. Methods: Breast cancer cell lines MCF-7, BT-474, MDA-MB-435 and SK-BR-3 were treated with differing enzastaurin concentrations. Western-Blot analyses were performed to examine PKCβ, phospho-GSK3β and caspase 9 expressions. The phenotype and proliferation of enzastaurin-treated cells were also monitored by fluorescence microscopy. Results: Treating all 4 cancer cell lines with ascending enzastaurin doses (0.1–10 μM) led to a significant downregulation of GSK3β phosphorylation (2–17%) compared to control cells. A 48–72 hr incubation with increasing enzastaurin doses also reduced the PKCβ expression significantly (5–50%). Moreover, a dose- dependent reduction of cell proliferation to levels of 15–40% compared to control cells with the highest enzastaurin concentration was detectable. We also saw a marked pro-caspase 9 reduction (0–30%) after enzastaurin compared to control cells. The microscopic inspection of treated cells phenotypically confirmed increasing apoptosis-induced cell death. Conclusions: Enzastaurin has a significant antiproliferative effect in different breast cancer cells. Moreover, enzastaurin suppresses GSK3β phosphorylation, suggesting that it may be a reliable pharmacodynamic marker for enzastaurin activity in breast cancer cells; however, more preclinical analysis is needed. Our study provides evidence for enzastaurin’s potential to directly suppress breast cancer cell proliferation and to induce tumor cell death by apoptotic induction. No significant financial relationships to disclose.

scholarly journals Role of WISP-2/CCN5 in the Maintenance of a Differentiated and Noninvasive Phenotype in Human Breast Cancer Cells

2007 ◽  
Vol 28 (3) ◽  
pp. 1114-1123 ◽  
Author(s):  
Asmaà Fritah ◽  
Cécile Saucier ◽  
Olivier De Wever ◽  
Marc Bracke ◽  
Ivan Bièche ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Tissue Growth ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

ABSTRACT WISP-2/CCN5 is an estrogen-regulated member of the “connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed” (CCN) family of the cell growth and differentiation regulators. The WISP-2/CCN5 mRNA transcript is undetectable in normal human mammary cells, as well as in highly aggressive breast cancer cell lines, in contrast with its higher level in the breast cancer cell lines characterized by a more differentiated phenotype. We report here that knockdown of WISP-2/CCN5 by RNA interference in estrogen receptor alpha (ERα)-positive MCF-7 breast cancer cells induced an estradiol-independent growth linked to a loss of ERα expression and promoted epithelial-to-mesenchymal transdifferentiation. In contrast, forced expression of WISP-2/CCN5 directed MCF-7 cells toward a more differentiated phenotype. When introduced into the poorly differentiated, estrogen-independent, and invasive MDA-MB-231 breast cancer cells, WISP-2/CCN5 was able to reduce their proliferative and invasive phenotypes. In a series of ERα-positive tumor biopsies, we found a positive correlation between the expression of WISP-2/CCN5 and ID2, a transcriptional regulator of differentiation in normal and transformed breast cells. We propose that WISP-2/CCN5 is an important regulator involved in the maintenance of a differentiated phenotype in breast tumor epithelial cells and may play a role in tumor cell invasion and metastasis.

scholarly journals Enhanced Cytotoxic Activity of Docetaxel-Loaded Silk Fibroin Nanoparticles against Breast Cancer Cells

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1416
Author(s):  
Ahmed Al Saqr ◽  
Shahid Ud Din Wani ◽  
H. V. Gangadharappa ◽  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Silk Fibroin ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

Despite decades of research, breast cancer therapy remains a great challenge. Docetaxel is an antimicrotubule agent that is effectively used for the treatment of breast cancer. However, its clinical use is significantly hampered by its low water solubility and systemic toxicity. The current study was designed to prepare docetaxel (DXL)-loaded silk-fibroin-based nanoparticles (SF-NPs) and to screen their potential antitumor activity against breast cancer cell lines. DXL-loaded SF-NPs were prepared using a nanoprecipitation technique and were evaluated for particle size, zeta potential, entrapment efficiency, and in vitro release profile. In addition, DXL-loaded SF-NPs were screened for in vitro cytotoxicity, cellular uptake, and apoptotic potential against MCF-7 and MDA-MB-231 breast cancer cell lines. The prepared DXL-loaded SF-NPs were 178 to 198 nm in diameter with a net negative surface charge and entrapment efficiency ranging from 56% to 72%. In vitro release studies exhibited a biphasic release profile of DXL from SF-NPs with sustained drug release for 72 h. In vitro cell studies revealed that entrapment of DXL within SF-NPs significantly improved cytotoxic potential against breast cancer cell lines, compared to the free drug, and enhanced cellular uptake of DXL by breast cancer cells. Furthermore, the accumulation in the G2/M phase was significantly higher in cells treated with DXL-loaded SF-NPs than in cells treated with free DXL. Collectively, the superior antitumor activities of DXL-loaded SF-NPs against breast cancer cells, compared to free DXL, could be ascribed to improved apoptosis and cell cycle arrest. Our results highlighted the feasibility of using silk fibroin nanoparticles as a nontoxic biocompatible delivery vehicle for enhanced therapeutic outcomes in breast cancer.

Sign in / Sign up

Export Citation Format

Share Document