scholarly journals Comparative effect of thermo/pH-responsive polymer-coated gold nanocages and hollow nanostars on chemo-photothermal therapy of breast cancer cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Asrin Pakravan ◽  
Mehdi Azizi ◽  
Fariborz Rahimi ◽  
Farhad Bani ◽  
Farideh Mahmoudzadeh ◽  
...  

Abstract Background Combination chemo-photothermal therapy appears to be one of the next generations of cancer treatment. In this study hollow gold nanostars (HGNSs) and gold nanocages (GNCs) were synthesized and stabilized with thermo-pH-sensitive thiol-end capped ABC triblock copolymer poly(acrylic acid)-b-poly(N isopropylacrylamide)-b-poly (e-caprolactone)-SH; PAA-b-PNIPAAm-b-PCL-SH (GNSs@Pol). Doxorubicin (Dox) was conjugated to the GNSs@Pol nanostructures via ionic interaction, covalent attachment and hydrogen bonding (GNSs@Dox-Pol). The physicochemical characteristics of prepared GNSs@Pol and GNSs were assessed using dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta potential techniques. Cytocompatibility of the GNSs@Pol was studied by hemolysis assay and MTT assay. The chemo-photothermal therapy (PTT) potential of GNSs@Dox-Pol was compared on MCF7 cells using MTT assay, cell cycle, DAPI staining and Annexin-V apoptosis assay techniques. Results Cell internalization results showed an almost complete uptake of GNSs@Pol by MCF-7 cells in the first 3 h of treatment. The heat generation measurement results showed that both of GNSs have a potential for light to heat conversion (∆T = 23–27 ºC) and HGNSs demonstrated better efficiency than GNCs after 10-min exposure to NIR irradiation. Following chemo-photothermal treatment, the highest cell mortality (90%) and apoptotic effects (97% apoptosis) were observed in HGNSs@Dox-Pol received laser irradiation treatment group. Conclusions This work highlights the potential application of designed GNSs@Dox-Pol in a combinational chemo-PTT to treat breast cancer cells. Graphic abstract

ACS Nano ◽  
2008 ◽  
Vol 2 (8) ◽  
pp. 1645-1652 ◽  
Author(s):  
Leslie Au ◽  
Desheng Zheng ◽  
Fei Zhou ◽  
Zhi-Yuan Li ◽  
Xingde Li ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatemeh Yousefimehr ◽  
Saeed Jafarirad ◽  
Roya Salehi ◽  
Mohammad Sadegh Zakerhamidi

AbstractIn this study, we report a facile green-synthesis route for the fabrication of reduced graphene oxide (rGO) using biomass of Brassica oleracea var. gongylodes (B. oleracea). In addition, we have attempted to provide a green synthesis approach to prepare Gold nanoparticles (Au NPs) on the surface of rGO by using stem extract of B. oleracea. The synthesized Au/rGO nanocomposite was evaluated using UV–visible and FTIR spectroscopy, XRD, Raman, FE-SEM, EDX, AFM and DLS techniques. The obtained results demonstrated that the synthesized Au NPs on the surface of rGO was spherical with sizes ranging about 12–18 nm. The Au/rGO NC was, also, developed as photo-synthesizer system for the photothermal therapy (PTT) of MCF7 breast cancer cells. The near-infrared (NIR) photothermal properties of Au/rGO NCs was evaluated using a continuous laser at 808 nm with power densities of 1 W.cm−2. Their photothermal efficacy on MCF7 breast cancer cells after optimizing the proper concentration of the NCs were evaluated by MTT assay, Cell cycle and DAPI staining. In addition, the potential of the synthesized Au/rGO NCs on reactive oxygen species generating and antioxidant activity were assessed by DPPH. Au/rGO NCs possess high capacity to light-to-heat conversion for absorption in range NIR light, and it is able to therapeutic effects on MCF7 cells at a low concentration. The maximum amount of cell death is 40.12% which was observed in treatment groups that received a combination of Au/rGO NCs and laser irradiation. The results demonstrate that the nanomaterials synthesized by green approach lead to efficient destruction of cancer cell and might thus serve as an excellent theranostic agent in Photothermal therapy applications.


Author(s):  
Siti N.H. Muhammad ◽  
Nik S. Yaacob ◽  
Nur A.M. Safuwan ◽  
Agustine N. Fauzi

Background: Survival and progression of cancer cells are highly dependent on aerobic glycolysis. Strobilanthes crispus has been shown to have promising anticancer effects on breast cancer cells. The involvement of the glycolysis pathway in producing these effects is unconfirmed, thus further investigation is required to elucidate this phenomenon. Objective: This study aims to determine the effect of S. crispus active fraction (F3) and its bioactive components on glycolysis in triple-negative breast cancer cells (MDA-MB-231). Methods: This study utilizes F3, lutein, β-sitosterol, and stigmasterol to be administered in MDA-MB-231 cells for measurement of antiglycolytic activities through cell poliferation, glucose uptake, and lactate concentration assays. Cell proliferation was assessed by MTT assay of MDA-MB-231 cells after treatment with F3 and its bioactive components lutein, β-sitosterol, and stigmasterol. The IC50 value in each compound was determined by MTT assay to be used in subsequent assays. The determination of glucose uptake activity and lactate concentration were quantified using fluorescence spectrophotometry. Results: Antiproliferative activities were observed for F3 and its bioactive components, with IC50 values of 100 µg/mL (F3), 20 µM (lutein), 25 µM (β-sitosterol), and 90 μM (stigmasterol) in MDA-MB-231 cells at 48 h. The percentage of glucose uptake and lactate concentration in MDA-MB-231 cells treated with F3, lutein, or β sitosterol were significantly lower than those observed in the untreated cells in a time-dependent manner. However, treatment with stigmasterol decreased the concentration of lactate without affecting the glucose uptake in MDA-MB-231 cells. Conclusion: The antiglycolytic activities of F3 on MDA-MB-231 cells are attributed to its bioactive components.


2019 ◽  
Vol 20 (22) ◽  
pp. 5626 ◽  
Author(s):  
Pierre Avril ◽  
Luciano Vidal ◽  
Sophie Barille-Nion ◽  
Louis-Romée Le Nail ◽  
Françoise Redini ◽  
...  

Background: Considering the positive or negative potential effects of adipocytes, depending on their lipid composition, on breast tumor progression, it is important to evaluate whether adipose tissue (AT) harvesting procedures, including epinephrine infiltration, may influence breast cancer progression. Methods: Culture medium conditioned with epinephrine-infiltrated adipose tissue was tested on human Michigan Cancer Foundation-7 (MCF7) breast cancer cells, cultured in monolayer or in oncospheres. Lipid composition was evaluated depending on epinephrine-infiltration for five patients. Epinephrine-infiltrated adipose tissue (EI-AT) or corresponding conditioned medium (EI-CM) were injected into orthotopic breast carcinoma induced in athymic mouse. Results: EI-CM significantly increased the proliferation rate of MCF7 cells Moreover EI-CM induced an output of the quiescent state of MCF7 cells, but it could be either an activator or inhibitor of the epithelial mesenchymal transition as indicated by gene expression changes. EI-CM presented a significantly higher lipid total weight compared with the conditioned medium obtained from non-infiltrated-AT of paired-patients. In vivo, neither the EI-CM or EI-AT injection significantly promoted MCF7-induced tumor growth. Conclusions: Even though conditioned media are widely used to mimic the secretome of cells or tissues, they may produce different effects on tumor progression, which may explain some of the discrepancy observed between in vitro, preclinical and clinical data using AT samples.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mehdi Agha Gholizadeh ◽  
Fatemeh T. Shamsabadi ◽  
Ahad Yamchi ◽  
Masoud Golalipour ◽  
Gagan Deep Jhingan ◽  
...  

Abstract Background The X-linked inhibitor of apoptosis protein (XIAP) is the most potent caspase inhibitor of the IAP family in apoptosis pathway. This study aims to identify the molecular targets of XIAP in human breast cancer cells exposed to XIAP siRNA by proteomics screening. The expression of XIAP was reduced in MCF-7 breast cancer cells by siRNA. Cell viability and the mRNA expression level of this gene were evaluated by MTS and quantitative real-time PCR procedures, respectively. Subsequently, the XIAP protein level was visualized by Western blotting and analyzed by two-dimensional (2D) electrophoresis and LC–ESI–MS/MS. Results Following XIAP silencing, cell proliferation was reduced in XIAP siRNA transfected cells. The mRNA transcription and protein expression of XIAP were decreased in cells exposed to XIAP siRNA than si-NEG. We identified 30 proteins that were regulated by XIAP, of which 27 down-regulated and 3 up-regulated. The most down-regulated proteins belonged to the Heat Shock Proteins family. They participate in cancer related processes including apoptosis and MAPK signaling pathway. Reduced expression of HSP90B1 was associated with apoptosis induction by androgen receptor and prostate specific antigen. Suppression of XIAP resulted in the enhancement of GDIB, ENO1, and CH60 proteins expression. The network analysis of XIAP-regulated proteins identified HSPA8, HSP90AA1, ENO1, and HSPA9 as key nodes in terms of degree and betweenness centrality methods. Conclusions These results suggested that XIAP may have a number of biological functions in a diverse set of non-apoptotic signaling pathways and may provide an insight into the biomedical significance of XIAP over-expression in MCF-7 cells.


2014 ◽  
Vol 21 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Anika Nagelkerke ◽  
Anieta M Sieuwerts ◽  
Johan Bussink ◽  
Fred C G J Sweep ◽  
Maxime P Look ◽  
...  

Lysosome-associated membrane protein 3 (LAMP3) is a member of the LAMP-family of proteins, which are involved in the process of autophagy. Autophagy is induced by tamoxifen in breast cancer cells and may contribute to tamoxifen resistance. In this study, the significance of LAMP3 for tamoxifen resistance in breast cancer was examined. The methods employed included use of clonogenic assays to assess the survival of MCF7 breast cancer cells with LAMP3 knockdown after tamoxifen treatment and of quantitative real-time PCR of LAMP3 to evaluate its predictive value for first-line tamoxifen treatment in patients with advanced breast cancer. Results show that tamoxifen treatment of MCF7 cells induced LAMP3 mRNA expression. LAMP3 knockdown in these cells increased tamoxifen sensitivity. Evaluation of expression of the autophagy markers, LC3B and p62, after LAMP3 knockdown showed increased expression levels, indicating that cells with LAMP3 knockdown have a suppressed ability to complete the autophagic process. In addition, knockdown of autophagy-associated genes resulted in sensitization to tamoxifen. Next, tamoxifen-resistant MCF7 cells were cultured. These cells had a sevenfold higher LAMP3 mRNA expression, showed elevated basal autophagy levels, and could be significantly resensitized to tamoxifen by LAMP3 knockdown. In patients treated with first-line tamoxifen for advanced disease (n=304), high LAMP3 mRNA expression was associated with shorter progression-free survival (P=0.003) and shorter post-relapse overall survival (P=0.040), also in multivariate analysis. Together, these results indicate that LAMP3 contributes to tamoxifen resistance in breast cancer. Tamoxifen-resistant cells are resensitized to tamoxifen by the knockdown of LAMP3. Therefore, LAMP3 may be clinically relevant to countering tamoxifen resistance in breast cancer patients.


2019 ◽  
Author(s):  
Daniela Hühn ◽  
Pablo Martí-Rodrigo ◽  
Silvana Mouron ◽  
Catherine S. Hansel ◽  
Kirsten Tschapalda ◽  
...  

ABSTRACTEstrogen receptor (ER)-positive breast tumors are routinely treated with estrogen-depriving therapies. Despite their effectiveness, patients often progress into a more aggressive form of the disease. Through a chemical screen oriented to identify chemicals capable of inducing the expression of the immune-checkpoint ligand PD-L1, we found antiestrogens as hits. Subsequent validations confirmed that estrogen deprivation or ERα depletion induces PD-L1 expression in ER-positive breast cancer cells, both in vitro and in vivo. Likewise, PD-L1 expression is increased in metastasis arising from breast cancer patients receiving adjuvant hormonal therapy for their local disease. Transcriptome analyses indicate that estrogen deprivation triggers a broad immunosuppressive program, not restricted to PD-L1. Accordingly, estrogen deprived MCF7 cells are resistant to T-cell mediated cell killing, in a manner that can be reverted by estradiol. Our study reveals that while antiestrogen therapies effectively limit tumor growth in ER-positive breast cancers, they also trigger a transcriptional program that favors immune evasion.


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