scholarly journals Selective Toxicity of Biosynthesised Silver Nanoparticles on MCF-7 and MDA MB-231 Breast Cancer Cell Lines

2019 ◽  
Vol 12 (6) ◽  
pp. 7-16
Author(s):  
Annie Aglin A ◽  
P Shruthi ◽  
S Subathra

Biosynthesized nanoparticles have many applications in the field of biopharmaceutics due to its high surface to volume ratio, less toxicity and synergistic effects with conjugated biomolecules. This study reports the selective cytotoxicity effect of biosynthesized silver nanoparticles (AgNPs) on breast cancer cell lines MCF-7 and MDA MB-231. AgNPs were synthesized using an aqueous extract of Mollugo cerviana species of plant and characterized using UV–visible spectroscopy, zeta potential analyser, SEM, FT-IR, XRD, and EDX. An UV-visible spectrum of the extract shows the surface plasmon resonance peak of AgNPs at 420 nm. SEM analysis results confirm the sphericity of the AgNPs whose size isin the range of 50 – 100 nm. The zeta potential value of -27 mV indicates the stability of the biosynthesized AgNPs. Dose-Dependent cytotoxicity was observed against human breast cancer cells lines MCF-7 and MDA MB-231. The inhibitory concentrations (IC50) are 21.53 μg/mL and 25.52 μg/mL respectively. There was no significant toxicity against Vero cells below 100 μg/mL concentration of AgNPs. The data obtained in the study reveal the potential therapeutic value of biogenic silver nanoparticles in cancer treatment and further studies are required to elucidate the mechanism of selective activity of biosynthesized AgNPs on cancer cells.

Author(s):  
Xiaodan Zhu ◽  
Lu Zhao ◽  
Jianliang You ◽  
Yiqun Ni ◽  
Zhipeng Wei ◽  
...  

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.


Author(s):  
Norma Lizeth Galindo-Alvarez ◽  
Humberto L. Mendoza-Figueroa ◽  
Martha Cecilia Rosales-Hernández ◽  
Norbert Bakalara ◽  
José Correa-Basurto

Background: A preliminary study of the biotransformation by cytochrome P450 enzymes (CYP) of N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), an HDAC inhibitor, led to the synthesis of two hydroxylated derivatives: N-(2,4-dihydroxyphenyl)-2-propylpentanamide (5a) and N-(2,5-dihydroxyphenyl)-2-propylpentanamide (5b). Objective: The study aims to evaluate the anti-proliferative activity of these di-hydroxylated derivatives in breast cancer cell lines. Methods: MTT assays were conducted in MCF-7 and MDA-MB-231 cell lines. Additionally, in silico studies were carried out to evaluate the affinity of these derivatives with the HDAC1 enzyme. Results: Results showed that only 5b possess an enhanced anti-proliferative effect in breast cancer cell lines MCF-7 and MDA-MB-231. Docking studies revealed that the presence of hydroxyl groups, as well as the position of the additional hydroxyl groups, could have an impact on HDAC1 affinity and could explain the lack of activity of compound 5a. Conclusion: A priori, these results hypothesize that anti-proliferative activity of 5b could be related to HDAC1 inhibition and thus anti-proliferative activity in breast cancer cells.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2089-2089
Author(s):  
Gheath Alatrash ◽  
Elizabeth Mittendorf ◽  
Anna Sergeeva ◽  
Pariya Sukhumalchandra ◽  
Na Qiao ◽  
...  

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.


2007 ◽  
Vol 28 (3) ◽  
pp. 1114-1123 ◽  
Author(s):  
Asmaà Fritah ◽  
Cécile Saucier ◽  
Olivier De Wever ◽  
Marc Bracke ◽  
Ivan Bièche ◽  
...  

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.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5139-5139 ◽  
Author(s):  
Abhishek Dhawan ◽  
Jens Friedrichs ◽  
Laura Bray ◽  
Lorenz C. Hofbauer ◽  
Manja Wobus ◽  
...  

Abstract Introduction The bone marrow microenvironment regulates the self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs), through a network dependent on cell-cell interaction. This interaction is mediated by morphogens, the extracellular matrix and cell adhesion molecules expressed and secreted by various cell types in the HSPC niche. Mesenchymal stromal cells (MSCs), as the major cellular component, maintain the stemness properties of the niche. The microenvironment thus becomes conducive for HSPCs to remain quiescent, thereby enabling long term self-renewal. Therefore, the safe haven in the bone marrow microenvironment and its constituent cell types can be targeted during tumorigenesis, thus making the niche neoplastic. Dissemination of breast cancer cells into the bone marrow has been described even in the early stages of the disease. The present study focuses on the influence of breast carcinomas on the genetic and functional profile of mesenchymal and hematopoietic progenitor cells of the bone marrow niche. Methods In vitro coculture models of breast cancer cell lines- MDA-MB231, MCF-7 and primary MSCs derived from the bone marrow of healthy donors were used in the study. Atomic- force microscopy based single-cell force spectroscopy (AFM-SCFS) and fluorescence based assays were used for cell adhesion experiments. Hydrogel based culture systems were used for 3-dimensional cocultures of breast cancer cells and MSCs. Hypoxic and normoxic culture conditions (0.5% and 20% oxygen respectively) were used for the experiments. Results The breast cancer cell lines caused a significant reduction in HSPC adhesion to MSCs (88% by MDA-MB 231 cells; p<0.005 and 73% by MCF-7 cells; p<0.005). AFM-SCFS studies also indicated a higher binding force between breast cancer cells and MSCs, as compared to HSPCs (MDA-MB231 cells-0.13nN, MCF-7 cells-0.074nN and HSPCs-0.05nN). MDA-MB231and MCF-7 cells express Intercellular adhesion molecule-1(ICAM-1), which has been shown to promote breast cancer metastasis (Hanlon et al, 2002; Rosette et al, 2005; Schröder C. et al, 2011). There was a significant difference in reduction of HSPC adhesion towards MSCs by ICAM-1 knockdown (ICAM-1 KD) tumor cells as compared to MDA-MB231 cells (84.83% by MDA-MB231 cells versus 28.11% by ICAM-1KD tumor cells, p<0.001). AFM-SCFS studies also showed a reduced binding force between ICAM-1 KD tumor cells and MSCs as compared to MDA-MB231cells (MDA-MB231 cells-0.14nN versus ICAM-1-KD tumor cells-0.05nN, p value<0.001). ICAM-1 KD studies thus showed that reduction in HSPC adhesion to MSCs by breast cancer cells was mediated through ICAM-1 signaling. A cytokine array was performed to investigate if breast cancer cell lines affect the cytokine profile of MSCs. The array showed altered expression of growth factors- Basic fibroblast growth factor (bFGF) and Platelet derived growth factor–beta (PDGF-BB) (2.2 fold upregulation and 0.5 fold downregulation in breast cancer cells- MSC cocultures respectively). Based on the array, a bFGF-mediated increase in the proliferation of MSCs and breast cancer cells in coculture was observed. The bFGF upregulation also caused an increased migration of MDA-MB231 cells towards MSCs in a transwell migration assay. An upregulation in the phosphorylation status of Akt was observed in breast cancer cells – MSC cocultures, as a downstream effect of upregulated bFGF levels. The bFGF-mediated increase in the proliferation of breast cancer cells and MSCs in coculture was shown to be dependent on the activation of PI3K-Akt pathway. The bFGF- mediated increase in the migration of MDA-MB231 cells towards MSCs was also inhibited upon addition of the PI3K blocker. Interestingly, the breast cancer cells caused a reduction in osteoblastic differentiation of MSCs by downregulation of PDGF-BB. Studies with 3-dimensional cocultures of breast cancer cells and MSCs also showed a reduction in osteoblastic differentiation of MSCs. Furthermore, long-term cocultures of breast cancer cells, HSPCs and MSCs showed reduced support for primitive HSPCs in the neoplastic niche. Conclusions These findings indicate a perturbed HSPC niche upon tumor invasion. The possible role of altered cytokine expression, consecutive downstream signaling in niche activation and bone turnover will be further studied using in vitro and in vivo approaches to recapitulate tumor micrometastases to the HSPC niche. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Gulsum Abusoglu ◽  
Bahadir Ozturk

AbstractObjectivesStatic magnetic field (SMF) was previously in practice for the therapy of some diseases and it has been thought that it may be a reliable supportive technique. The aim of this study was to find out the synergistic effect of SMF administration with flavonoids in terms of apoptosis on breast cancer cell lines.Material and methodsThe effects of flavonoids on the proliferation of breast cancer cell lines were observed by MTT cell viability test. The cells were treated with SMF + hesperetin and SMF + quercetin. Apoptosis rates and Bax, Bcl-2 protein levels were detected by flow cytometer and Western Blot, respectively.ResultsCell lines were treated with quercetin and quercetin + SMF, substantial amount of cells [3.96, 4.86, 11.40% for MCF-7 and MDA MB-231 cell lines, respectively (p<0.001)] were mainly in the apoptotic phase. The apoptosis rates of hesperetin and hesperetin + SMF were 2.53, 6.06, 10.10% (p<0.001) for MCF-7 and MDA MB-231 cell lines, respectively. Bax:Bcl-2 ratios were significantly increased after flavonoids + SMF exposure (2.7 vs. 1.6 fold (p<0.0001) in hesperetin + SMF group and 1.8 vs. 1.3-fold (p<0.0001) in quercetin + SMF group for MCF-7 and MDA MB-231 cell lines, respectively.ConclusionsSMF might support the anti-cancer properties of flavonoids, on breast cancer cells via mitochondria-related apoptosis pathway.


2016 ◽  
Vol 62 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Z.N. Nikiforova ◽  
M.A. Taipov ◽  
I.A. Kudryavcev ◽  
V.E. Shevchenko

Breast cancer is the most frequent cancer and the leading cause of cancer-related deaths in women worldwide. We determined the expression of COX2, COX1, 15-HPGDH mRNA and miRNAs (miR-21, miR-155) in three estrogen positive human breast cancer cell lines (MCF-7, BT-474, ZR-75-1). According to the results of three independent experiments the amount of COX1 and COX2 mRNA was significantly higher in the ZR-75-1 than in MCF-7 and BT-474 cells. Levels of total 15-HPGDH; functional 15-HPGDH mRNA in BT-474 cell line were lower than in MCF-7 and ZR-75-1 ones. The synthesis of 15-HPGDH enzyme in BT-474 line was blocked at the nuclear immature pre-mRNA processing level. miR-155 expression level was significantly lower than miR-21 in breast cancer cell lines. Correlations between the dysregulation of miR-21, miR-155 and 15-HPGDH, COX-1, COX-2 mRNA were identified. Expression of miR-21 was high in MCF-7, ZR-75-1 and BT-474 cell lines. Our results show that miR-21 and miR-155 regulate activity of several genes in cancer cells, their effect on the individual genes was in some cases cumulative. Based on our results, we concluded that miR-21, miR-155 suppress the work of tumor suppressor gene 15-HPGDH and induce potential oncogene COX-2 that promotes cell malignancy and metastasis of breast cancer.


2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity


2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary

Background:Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.Methods:The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.Results:Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.Conclusion:These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.


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