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Antimicrobial peptides, such as nisin, are proposed as promising agents for cancer treatment. While glycation has been recognized as an effective method for enhancing various physicochemical properties of nisin, its anticancer effects remain unexplored. Therefore, we aimed to assess the anticancer potential of glycated nisin against MDA-MB-231 cells. The MDA-MB cells were treated with increasing concentrations of nisin and glycated nisin for 24, 48, and 72 h. The IC50 values for nisin were higher than those for glycated nisin. Glycated nisin at concentrations of 20 and 40 µg/mL decreased cell viability more than nisin at the same concentrations. The rate of apoptosis in the group treated with 20 µg/mL of nisin was lower compared to other treatment groups, and no significant difference in apoptosis rates was observed at different time points (p > 0.05). However, in the glycated nisin groups with concentrations of 10, 20, and 40 µg/mL, the level of apoptosis was very high after 24 h (73-81% of cells undergoing apoptosis). Overall, our study suggests that glycated nisin exhibits stronger cytotoxic effects on MDA-MB-231 cells, primarily involving the induction of apoptosis. This indicates its potential utilization as an alternative approach to address the issue of drug resistance in cancer cells., (© 2024. The Author(s).)

Radiation therapy and phototherapy are commonly used cancer treatments that offer advantages such as a low risk of adverse effects and the ability to target cancer cells while sparing healthy tissue. A promising strategy for cancer treatment involves using nanoparticles (NPs) in combination with radiation and photothermal therapy to target cancer cells and improve treatment efficacy. The synthesis of gold NPs (AuNPs) for use in biomedical applications has traditionally involved toxic reducing agents. Here we harnessed dopamine (DA)-conjugated alginate (Alg) for the facile and green synthesis of Au NPs (Au@Alg-DA NPs). Alg-DA conjugate reduced Au ions, simultaneously stabilized the resulting AuNPs, and prevented aggregation, resulting in particles with a narrow size distribution and improved stability. Injectable Au@Alg-DA NPs significantly promoted ROS generation in 4T1 breast cancer cells when exposed to X-rays. In addition, their administration raised the temperature under a light excitation of 808 nm, thus helping to destroy cancer cells more effectively. Importantly, no substantial cytotoxicity was detected in our Au@Alg-DA NPs. Taken together, our work provides a promising route to obtain an injectable combined radio enhancer and photothermally active nanosystem for further potential clinic translation., (© 2024. The Author(s).)

Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi 2 S 3 -Fe 3 O 4 , to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi 2 S 3 -Fe 3 O 4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi 2 S 3 @BSA-Fe 3 O 4 -FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi 2 S 3 @BSA-Fe 3 O 4 -FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi 2 S 3 @BSA-Fe 3 O 4 -FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area., Competing Interests: Declaration of competing interest J.C. is a co-founder and shareholder of TargTex S.A., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486-5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486-5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486-5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486-5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24 - CD44 + cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486-5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486-5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC., (Copyright © 2021. Published by Elsevier Masson SAS.)

The transcription factor high mobility group protein A2 (HMGA2) plays an important role in the pathogenesis of some cancers including breast cancer. Polyamidoamine dendrimer generation 4 is a kind of highly branched polymeric nanoparticle with surface charge and highest density peripheral groups that allow ligands or therapeutic agents to attach it, thereby facilitating target delivery. Here, methotrexate (MTX)- modified polyamidoamine dendrimer generation 4 (G4) (G4/MTX) was generated to deliver specific small interface RNA (siRNA) for suppressing HMGA2 expression and the consequent effects on folate receptor (FR) expressing human breast cancer cell lines (MCF-7, MDA-MB-231). We observed that HMGA2 siRNA was electrostatically adsorbed on the surface of the G4/MTX nanocarrier for constructing a G4/MTX-siRNA nano-complex which was verified by changing the final particle size and zeta potential. The release of MTX and siRNA from synthesized nanocomplexes was found in a time- and pH-dependent manner. We know that MTX targets FR. Interestingly, G4/MTX-siRNA demonstrates significant cellular internalization and gene silencing efficacy when compared to the control. Besides, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated selective cell cytotoxicity depending on the folate receptor expressing in a dose-dependent manner. The gene silencing and protein downregulation of HMGA2 by G4/MTX-siRNA was observed and could significantly induce cell apoptosis in MCF-7 and MDA-MB-231 cancer cells compared to the control group. Based on the findings, we suggest that the newly developed G4/MTX-siRNA nano-complex may be a promising strategy to increase apoptosis induction through HMGA2 suppression as a therapeutic target in human breast cancer.

MicroRNAs (miRNAs) have the ability to regulate gene expression programs in cells. Hence, altered expression of miRNAs significantly contributes to breast cancer development and progression. Here, we demonstrate that the miRNA miR-142-3p directly targets the 3' untranslated region of HMGA2, which encodes an onco-embryonic protein that is overexpressed in most cancers, including breast cancer. Down regulation of miR-142-3p predicting poor patient survival in grade 3 breast cancer (P-value = 0.045). MiR-142-3p downregulates HMGA2 mRNA and protein levels. Higher miR-142-3p and lower HMGA2 expressed are found in breast cancer versus normal breast tissue (P-value<0.05), and their levels inversely correlate in breast cancers (P-value = 1.46 × 10 -4 ). We demonstrate that miR-142-3p induces apoptosis and G2/M cell cycle arrest in breast cancer cells. In addition, it inhibits breast cancer stem cell properties and decreases SOX2, NANOG, ALDH and c-Myc expression. MiR-142-3p also decreases cell proliferation through inhibition of the ERK/AKT/STAT3 signaling pathways. Finally, pathway analyses of patient samples suggest that these mechanisms also acting in the tumors of breast cancer patients. Thus, our work identifies HMGA2 as a direct miR-142-3p target and indicates that miR-142-3p is an important suppressor of breast cancer oncogenesis. This identifies miR-142-3p may candidate as a therapeutic molecule for breast cancer treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.

Cancer cells escape immune destruction. From this perspective, myeloid-derived suppressor cells (MDSCs), which are immunosuppressive in various cancers including breast cancer (BC), are significant. However, the precise mechanisms are unknown. We isolated HLA-DR - CD33 + MDSCs and CD3 + T cells from BC patients' peripheral blood and healthy donors through MACS and immunophenotyped by flow cytometry. Transfection of short-interfering RNAs and treatment with a TLR7/8 agonist altered pathway activities in vitro . Gene expression was analyzed using qRT-PCR, western blotting, and immunohistochemistry. Our findings showed an association between the progression of BC and increased levels of circulating HLA-DR - CD33 + MDSCs. These cells strongly suppress both autologous and analogous CD3 + T cell proliferation and enter the tumor microenvironment. We also identified increased STAT3 signaling and increased IDO and IL-10 expression in BC-derived MDSCs as immunosuppression mechanisms. Further, STAT3 inhibition and TLR7/8 pathway stimulation reduce the immunosuppressive activity of patient-derived MDSCs on T cells by inducing MDSC repolarization and differentiation into mature myeloid cells. This also alters the expression of critical cytokines and transcription factors in CD3 + T cells and, importantly, reduces breast cancer cells' proliferation. Finally, while chemotherapy is able to significantly reduce circulating MDSCs' level in patients with breast cancer, these MDSCs remained highly T cell-suppressive. We identified a novel molecular mechanism of MDSC-mediated immunosuppression. STAT3 inhibition and TLR7/8 pathway stimulation in MDSCs repolarize and suppress MDSCs from breast cancer patients. This offers new opportunities for BC immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Safarzadeh, Mohammadi, Mansoori, Duijf, Hashemzadeh, Khaze, Kazemi, Derakhshani, Silvestris and Baradaran.)

Breast cancer is the most common women's malignancy in the world and, for subgroups of patients, treatment outcomes remain poor. Thus, more effective therapeutic strategies are urgently needed. MicroRNAs (miRNAs) have emerged as promising therapeutic tools and targets, as they play significant roles in regulating key cellular processes by suppressing gene expression. However, additive opportunities involving miRNAs have been underexplored. For example, both miR-34a and miR-200c individually suppress the development of different types of cancer, but the cellular effects of their combined actions remain unknown. Here, we show that miR-34a and miR-200c levels are reduced in breast tumors compared to adjacent normal tissues and that this additively predicts poor patient survival. In addition, in cell lines, miR-34a and miR-200c additively induce apoptosis and cell cycle arrest, while also inhibiting proliferation, invasion, migration, stemness and epithelial-to-mesenchymal transition (EMT). Mechanistically, both miRNA-34a and miR-200c directly target HIF1-α and subsequently downregulate VEGFR, MMP9 and CXCR4, although combined miRNA-34a and miR-200c delivery suppresses mouse xenograft tumor development as effectively as individual delivery. We establish a model, supported by in vitro and clinical data, which collectively suggest that the co-delivery of miR-34a and miR-200c represents a promising novel therapeutic strategy for breast cancer patients.

Breast cancer (BC) is the most common cancer among women that is responsible for the most of the cancer-related death in worldwide. Drug resistance is remaining as a significant clinical obstacle to treat BC patients effectively. Therefore, to help overcome this problem, it is necessary to understand the mechanisms of drug resistance. microRNAs classify as highly conserved non-coding RNAs (~22 nucleotides) and interact with mRNAs-coding genes for direct post-transcriptional repression. It has been reported that miR-21 is overexpressed and also acts as oncomiR in many human malignancies by targeting of several tumor suppressor genes-associated with apoptosis, proliferation and metastasis. Specifically, it has been reported that miR-21 is responsible for the drug resistance and its overexpression is related to the development of Multi Drug Resistance (MDR) in breast cancer. In this review, we discussed about the role of miR-21 on the drug resistance of breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

During breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators high mobility group A2 (HMGA2) and BTB and CNC homology 1 (Bach-1) are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach-1 promote cancer development has been limited. We found that HMGA2 and Bach-1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach-1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach-1 knockdown additively decrease cell proliferation, migration, epithelial-to-mesenchymal transition, and colony formation, while promoting apoptotic cell death via upregulation of caspase-3 and caspase-9. First the first time, we show that HMGA2 and Bach-1 overexpression in tumors correlate positively and that the proteins cooperatively suppress a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity, and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer., (© 2019 Wiley Periodicals, Inc.)

Background: Breast cancer is the most common type of cancer among women, and despite improved treatments, it remains a major challenge. However, improved mechanistic insight may lead to novel therapeutic strategies. miR-142-3p belongs to the miR-142 family and is involved in pathogenesis and metastasis of various types of malignancies by targeting several important messenger RNAs (mRNAs) including Bach-1. This is especially true for breast cancer, where Bach-1 is involved in the metastatic spread by deregulation of metastasis-associated genes., Methods: In this study, we collected 24 breast cancer tissues with 24 adjusted normal tissues to measure the expression levels of miR-142-3p and Bach-1 mRNA using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and IHC. miR-142-3p targeting of Bach-1 expression in MCF-7 and MDA-MB-468 breast cancer cells was evaluated using bioinformatics, qRT-PCR and western blot analyses. The cellular proliferation, invasion, and migration were assessed by MTT, transwell matrigel and wound healing assay and the EMT-associated proteins C-X-C chemokine receptor type 4 (CXCR-4), matrix metalloproteinase-9 (MMP9), and vascular endothelial growth factor receptor (VEGFR) were analyzed by western blot analysis. Also, the expression levels of tumor suppressors including miR-330, miR-145, and miR-34a were estimated by qRT-PCR., Results: Analysis of paired specimens of primary malignant and normal tissues showed that miR-142-3p was downregulated, while Bach-1 mRNA and protein both were overexpressed in the breast cancer tumors. This inverse relationship was confirmed by cell line experiments demonstrating that miR-142-3p expression reduced Bach-1 mRNA levels. Furthermore, replacement of miR-142-3p could inhibit the proliferation, invasion, and migration in breast cancer potentially by targeting of Bach-1 mRNA and subsequent inhibition of CXCR4, MMP9, and VEGFR protein expressions. In addition, induction of miR-142-3p could upregulate tumor suppressor miRNAs, including miR-330, miR-145, and miR34a., Conclusion: For the first time, our results revealed that miR-142-3p could target Bach-1in breast cancer cells leading to the reduction of EMT-related proteins and reduced cell proliferation, invasion, and migration. The results also demonstrated that miR-142-3p could regulate important tumor suppressor miRNAs in breast cancer cells. In conclusion, our results suggest that miR-142-3p could be a good candidate for the targeted therapy of breast cancer, especially for the invasive type., (© 2018 Wiley Periodicals, Inc.)

MicroRNAs (miRNAs) regulate several biological and physiological processes in mammalian cells, including cellular proliferation, differentiation, apoptosis, and metabolism. Recent studies have confirmed the alteration of them during the cancer development. Matrix metalloproteinases (MMPs), belonging to the large family of proteases, have also been demonstrated to play crucial roles in tissue remodeling, and to support cancer progression and metastasis. There are several known miRNAs which regulate the MMP family and their expression. The expression profiles of miRNAs involved in MMP regulation, change during cancer progression, and metastasis. The present review focuses on important miRNAs capable of targeting MMPs through direct and indirect interactions during the breast cancer development, progression, and metastasis., (© 2018 Wiley Periodicals, Inc.)

Evading immune destruction is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3 + T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA-DR - CD33 + MDSCs in peripheral blood is about 10-fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA-DR - CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient-derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient-derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC., (© 2018 Wiley Periodicals, Inc.)

Background: Breast cancer has a high prevalence among women worldwide. Tumor invasion and metastasis still remains an open issue that causes most of the therapeutic failures and remains the prime cause of patient mortality. Hence, there is an unmet need to develop the most effective therapeutic approach with the lowest side effects and highest cytotoxicity that will effectively arrest or eradicate metastasis., Methods: An MTT assay and scratch test were used to assess the cytotoxicity and migration effects of Urtica dioica on the breast cancer cells. The QRT-PCR was used to study the expression levels of miR-21, MMP1, MMP9, MMP13, CXCR4, vimentin, and E-cadherin., Results: The results of gene expression in tumoral groups confirmed the overexpression of miR-21, MMP1, MMP9, MMP13, vimentin, and CXCR4, and the lower expression of E-cadherin compared to control groups (P<0.05). Moreover, the results of the MTT assay show that Urtica dioica significantly inhibited breast cancer cell proliferation. Moreover, findings from the scratch assay exhibited the inhibitory effects of Urtica dioica on the migration of breast cancer cell lines., Conclusion: Urtica dioica extract could inhibit cancer cell migration by regulating miR-21, MMP1, MMP9, MMP13, vimentin, CXCR4, and E-Cadherin. Moreover, our findings demonstrated that the extract could decrease miR-21 expression, which substantially lessens the overexpressed MMP1, MMP9, MMP13, vimentin, and CXCR4 and increases E-cadherin in the tumoral group., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: Breast adenocarcinoma is the second common cancer in women the incidence of which is increasing in many countries, especially in developing companies. In this study, miRNA143 has been replaced by vector based microRNA-143 in breast adenocarcinoma cells (MDA-MB-468) and its anti-cancer effects on breast adenocarcinoma cells have been evaluated., Methods: The pCMV-MIR-143 vector was transfected into MDA-MB-468 cells via JetPEI transfection reagent. The transfected cells were selected by IC50 concentration of Geneticin antibiotic (G418) after a 2-week treatment. To evaluate the effect of miR-143 on the inhibition of migration, scratch wound healing assay was performed. Then, the expression level of miR-143, Kras, Vimentin, CXCR4, MMP9 and E-Cadherin were measured by the qRT-PCR method., Results: Results of MTT and wound healing assays showed that miR-143 inhibited cell growth and cell migration in miR-143 induced cell line compared with control group. The result of gene expression showed that miR-143 reduced Kras, Vimentin, CXCR4 and MMP9 expression, and increased E-Cadherin expression in miR-143 replaced cells compared to control cells., Conclusion: The results showed that miRNA-143 plays an important role in cell growth and migration during breast cancer development and metastasis and it can be a candidate as a therapeutic molecule in microRNA replacement therapy of breast adenocarcinoma., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Despite the great improvements in clinical and therapeutic techniques in recent years, many advanced breast cancer patients still died of the postoperative recurrence and metastasis of disease. Bach1 plays a role in the development of the invasive phenotypes of cancer, cell division and apoptosis in tumor cells. The aim of this study was to investigate the effect of specific bach1 siRNAs, on the proliferation, migration, invasive, induction of apoptosis, cell cycle arrest and alter EMT related miRNA of MDA-MB-468 cells (breast cancer)., Methods: siRNA transfection was performed with transfection reagent. The expression levels of Bach1 mRNA and protein were measured by qRT-PCR and western blot analysis, respectively. The survival of cells was determined using MTT assay cells, apoptosis using Tunel assay, Cell migration using scratch assay and Cell cycle analysis by Propidium Iodide (PI) DNA staining method by using flow cytometry on the MDA-MB-468. The expression levels of MMP-9 and CXCR4 were measured by qRT-PCR., Results: Transfection with siRNA significantly suppressed the expression of bach1 gene in dose dependent manner after 48h (p<0.0001). Surprisingly, treatment with bach1 siRNA arrest cell cycle in S phases (p<0.0001). Moreover siRNA transfection had effects on breast adenocarcinoma cells and inhibits the migration (p<0.0001), proliferation (p<0.0001), cell cycle arrest (p=0.03) and induces apoptosis (p<0.0001) and reduces the expression of miR-21 (P=0.0014)., Conclusion: Our results suggest that the bach1 can be considered as a potent adjuvant in breast cancer therapy., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Chitosan-coated human serum albumin nanoparticles were functionalized by MUC1 aptamer to obtain a selective drug carrier toward cancers overexpressing MUC1. The negative charges of albumin nanoparticles were shifted to positive charges by surface modification with chitosan, and MUC1 was conjugated through an acrylate spacer. The cytotoxicity of targeted nanoparticles was significantly more than non-aptamer nanoparticles, and also the chitosan-coated nanoparticles had more cytotoxic effects than the negatively charged albumin nanoparticles. The IC 50 of targeted nanoparticles was 28 and 26% of free paclitaxel in MCF7 and T47D cells at 48h, respectively. Confocal laser scanning electron microscopy showed that aptamer conjugation and positive charge increase the cellular uptake. 66% of paclitaxel was released within 32h, but 100% of drug was released at pH=5.5 (similar cancer cells). The paclitaxel plasma amount was at a good level of 17.6% at 2h for increasing the chance of cellular uptake., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: The HMGI-C (high mobility group protein isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal proteins that can modulate transcription of an ample number of genes. Genome-wide studies reveal upregulation of the HMGI-C gene in many human cancers, which suggests that HMGI-C might play a critical role in the progression of various tumors. However, the exact role of HMGI-C in breast adenocarcinoma has not been made clear., Methods: HMGI-C mRNA expression in breast cancer samples and marginal normal tissues was characterized using qRT-PCR. The cytotoxic effects of HMGI-C siRNA on breast adenocarcinoma cells were determined using MTT assay. Relative HMGI-C mRNA and protein levels were measured by quantitative real-time PCR and western blotting, respectively. Apoptosis detection was done using TUNEL and Annexin-V/PI assays, P53, caspase 3, 9, 8 and Bcl2 proteins evaluated by protein gel blot and miR34a, Let-7a genes investigates by QRT-PCR assay. Cell cycle was analyzed by flow cytometry assay using propidium iodide DNA staining., Results: An overexpression of HMGA2 was revealed with highly statistically significant differences between breast cancer samples and marginal normal tissues (P < 0.0001). HMGI-C siRNA significantly reduced both mRNA and protein expression levels in a 48-hour period after transfection and in a dose-dependent manner. We observed that the knockdown of HMGI-C led to the significant induction of apoptosis via mitochondrial pathway by inducing miR34a and cell cycle arrest in MDA-MB-468 cells in vitro., Conclusions: These results propose that HMGI-C might play a critical role in the progression of breast adenocarcinoma. Here we introduced HMGI-C as a potential therapeutic target for trigger apoptosis and cell cycle arrest in human breast adenocarcinoma. Therefore HMGI-C siRNA may be an effective adjuvant in human breast adenocarcinoma.

Introduction: Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line., Materials and Methods: To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry., Results: Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1., Conclusions: Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

BACH1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1) is a transcriptional factor and a member of cap 'n' collar (CNC) and basic region leucine zipper factor family. In contrast to other bZIP family members, BACH1 appeared as a comparatively specific transcription factor. It acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative. In regard to studies lately, although, BACH1 has been related to the regulation of oxidative stress and heme oxidation, it has never been linked to invasion and metastasis. Recent studies have showed that BACH1 is involved in bone metastasis of breast cancer by up-regulating vital metastatic genes like CXCR4 and MMP1. This newly discovered aspect of BACH1 gene provides new insight into cancer progression study and stands on its master regulator role in metastasis process, raising the possibility of considering it as a potential target for cancer therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Breast cancer is the most common cause of cancer-related death among women in the whole world. MiR- 34a and let-7a are well known tumor suppressors that participate in the regulation of apoptosis, invasion and other cellular functions. In this study, expression of miR-34a, let-7a and apoptosis pathway genes such as Bcl-2, Caspase-3 and P53 were evaluated using quantitative real-time PCR in 45 paired samples of normal margin and tumor tissue collected from breast cancer patient at advanced stage (3-4). MiR-34a, let-7a, caspase-3 and P53 expression are reduced and Bcl-2 expression is increased within tumoral tissues in comparison with normal margin tissues. P53 expression directly or indirectly was correlated with miR-34a, let-7a, Bcl-2 and caspase-3 expression. In This study we found that MiR-34a and let-7a expression are reduced in the tumoral tissues. Down- regulation of these two molecules correlated with expression of genes associated with apoptosis. These results suggest that due to the correlation of miR-34a and let-7a with apoptotic and anti-apoptotic pathways these molecules could participate as regulators in advanced clinical stages of breast cancer and should be considered as markers for diagnosis, prognostic assessment and targeted therapy.