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In the current study, Mesoporous silica nanoparticles (MSNs) were provided and functionalized using zinc, amine, and graphene oxide (GO) (MZNG). Then, they were applied to deliver Doxorubicin, an anticancer drug, to breast cancer cells. The characterization findings indicated that MZNG loaded with DOX had a smooth surface and a spherical shape without homogeneous distribution with a particle size of around 215 nm. The high entrapment efficiency of DOX was observed for MZNGs at pH 7.4. Cytotoxicity results indicated that free DOX had high compatibility with HFF cells compared to DOX loaded into MZNG formulations, while DOX-loaded nanoparticles significantly increased the cytotoxicity against MDA-MB-231compared to free drugs and non-loaded nanoparticles. Moreover, DOX-loaded nanoparticles displayed increased apoptotic potential in MDA-MB-231 compared to free DOX and non-loaded nanoparticles (MZNGs). Upon treatment with samples, a downregulation of MMP-9 and Bcl-2 genes and an upregulation of Bax, Caspase 3, and Mir-193 genes were found. The prepared Nano-formulation holds great promise for treating breast cancer.

Breast cancer is divided into different subtypes based on molecular characteristics, among these subtypes, Triple-negative breast cancer, has the poorest prognosis and survival with invasive. In this study, TNBC cell line was used to explore crocin anti-metastatic effect on the Wnt/β-catenin pathway. Cell proliferation assessed by MTT assay and effects of crocin on migration monitored by transwell and wound healing experiments. Expression of certain epithelial-mesenchymal transition (EMT) markers genes was evaluated by real-time PCR. β-catenin expression also examined by real-time PCR. Findings revealed crocin significantly inhibits cell proliferation and migration of tumor cells in a dose-dependent manner. Moreover, crocin decreased the expression of Vimentin, Snail, Zeb-1 and β-catenin. Also, crocin increased the expression of E-cadherin in MDA-MB-231 cell line. Results showed an association between crocin and Wnt/β-catenin signaling pathway. In conclusion, this study establishes that crocin can be a promising therapeutic for triple-negative breast cancer.

This research aims to design and synthesize a drug contained nanocomposite papered with a new combination of chitosan (CS)-coated magnetic-gold core-shell (Fe3O4@Au) as curcumin (CU) delivery to treat breast cancer (MDA-MB-231) and normal (MCF10A) cell lines. The CU drug was encapsulated in this nanosystem. Folate (Fol) functionalization of this nanosystem for targeting therapy purposes led to the construction of the final Fe3O4@Au-CS-CU-Fol nanoformulation. The SPION@Au was achieved using Pulsed Laser Ablation in Liquid (PLAL) procedure by the 530 nm wavelength with various laser fluence (1.8, 2.3, and 2.6) J/cm2. The polymeric coating, drug encapsulation, and Fol functionalization processes were performed due to reverse microemulsion methods. This nanosystem was characterized by a dynamic light scattering (DLS) Atomic Force Microscope (AFM), Field Emission Scanning Electron Microscopy (FESEM), High-Resolution Transmission Electron Microscopy (HRTEM), UV-Visible spectrophotometer, and vibrating sample magnetometry (VSM). A new type of CU-loaded nanocarrier was synthesized, and its anti-tumor properties were evaluated against breast cancer cell lines in both in vitro and in vivo conditions. The obtained mean size of Fe3O4@Au nanoparticles (NPs) was 52.37, 60.24, and 72.45 nm at 1.8, 2.3, and 2.6 J/cm2, respectively. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay of drug-loaded NPs on the MDA-MB-231 cell line proved that the CU cytotoxicity effect could enhance when encapsulated in Fe3O4@Au-CS-Fol nanocarrier compared with void CU. On the other hand, the flow cytometry charts presented that this nanoformulation can enhance the remedial properties of CU due to apoptosis stimulation in the MDA-MB-231 cell line. The real-time polymerase chain reaction (PCR) analysis confirmed the activation of apoptosis in the cells treated with the Fe3O4@Au-CS-CU-Fol. The in vivo evaluation of the Fe3O4@Au-CS-CU-Fol nanosystem proved that the tumor volume reduces in a certain time. Close inspection of results confirmed that Fe3O4@Au-CS-CU-Fol exerts a significant chemo-preventive effect on breast cancer through cell viability index, apoptosis stimulation, and anti-tumor activity.

Diketopiperazines have attracted attention from the point of view of synthesis and biological properties for the treatment of various diseases, including cancer, although 2,6-DKPs have been less studied. In this work is present the inhibitory effects of various 2,6-DKPs derived from α-amino acids over the MDA-MB-231 triple-negative breast cancer cells by the MTT assay. It was found that IC50 values obtained for compounds 1 and (S) enantiomers were between 4.6 x 10− 3 and 4.944 (mM), where 1 and (S)-2a showed the lowest values, for (R) enantiomers were in the range 0.021 and 3.639 mM, where (R)-2b exhibited the lowest value. In addition, the apoptotic induction of the 2,6-DKPs was investigated over MDA-MB-231 cell line by flow cytometry, these results showed that all the compounds studied induced more apoptosis at 48 h than at 24 h in a range of 54.1 to 76.2%, except 12a that exhibited a 3% decrease compared to the 24 h test. According to the biological assays, all the evaluated 2,6-DKPs derivatives could be considered for further studies in vivo, principally those with the lowest IC50 value and (S) stereoisomers as possible antitumoral agents to mama cancer.

Chitosan-encapsulated ternary titanium dioxide-nickel oxide-copper oxide (CTNC) hybrid nanomaterials (HNM) were synthesis via a facile one-pot precipitation method. The synthesized Chitosan-titanium dioxide-nickel oxide-copper oxide was characterized by XRD, UV, FTIR, DLS, FESEM, EDAX, and PL tested against G- (gram-negative) bacterial strain such as K. pneumonia, S. dysenteriae, E. coli, P. Vulgaris, P. aeruginosa, and V. cholerae, employed by the well method. The CTNC hybrid nanomaterials exhibit a more substantial antibacterial effect against gram-negative bacteria. The MDA-MB-231 cell-line, with an IC50 concentration value of 9.8 g/mL was chosen to test CTNC hybrid nanomaterials' anticancer properties against human breast cancer cell lines. The toxicity studies of fibroblast L929 cells showed that the CTNC hybrid nanomaterials were less harmful to the healthy cells. As a result, the CTNC hybrid nanomaterials can be used for biomedical and industrial applications to improve human health conditions.

The chemical contents, antibiofilm and anticancer effects of different propolis extracts (petroleum ether, chloroform, ethyl acetate and methanol) collected from Mila (Algeria) were investigated in this study. Chemical analysis showed the presence flavonoids as a major compound. The highest antibiofilm activity was observed at the 200 µg/ml methanol fraction (92%). Florescent microscope images also confirmed antibiofilm effect. Our results showed that the structure of biofilm treated with propolis was degraded and there were no water channels seen in the biofilm structure. In addition, the density of dead cells in the biofilm was also noted with fluorescent staining. According to FTIR analysis, it was found that propolis caused some changes in macromolecules on the cell surface. Cytotoxic activity of propolis (EC50: 97–117 µg/ml) was determined by MTT test. Propolis extracts caused a significant increase in mRNA levels of proteins involved in tumor suppression and apoptosis in the MDA-MB-231 cell line and induced apoptosis. Western blot analysis confirmed these results. As a result, it can be said that Algerian propolis has anticancer and antibiofilm effective compounds.

In this work, first, copper oxide nanoparticles (CUO NPs) were synthesized by physical methods and then coated with the bovine serum albumin (BSA) via biologically meditated minerals to form CUO@BSA NPs. Finally, curcumin (CUR) as an anticancer drug were immobilized on the surface of CUO@BSA NPS. The properties of CUO@BSA-CUR NPS were investigated by FTIR, UV-Vis, TEM, and AFM spectroscopes. It was found that the synthesized CUO@BSA-CUR nanoparticles were spherical with a particle size of 20 to 30 nm and have a sustained release of CUR at 37°C in buffer solution. Also, the result of release in biological environment showed that maximum drug release rate for this nanocarrier in pH 7.4 was measured 75% after 48 hours. The cytotoxicity of CUO@BSA-CUR on MDA-MB-231 cell line was studied. The results showed that CUO@BSA-CUR nanoparticles have significant cytotoxic activity on this cell line, while the results of MTT assay indicated the CUO@BSA NPs have no toxicity effect on the cancer cells.

Polyoxometalates (POMs) are a class of inorganic cytotoxic agents with potential anticancer effects. As the nano-formulation is one of the best approaches to adjust the therapeutic effects along with selective delivery, in this study, a novel biocompatible nano-composite (NC) of Anderson-type manganese polyoxomolybdate (MnMo6) was prepared using chitosan conjugate to achieve better selective cytotoxicity profile.Imidazolium modified chitosan (CSIm) was utilizedto getthe MnMo6 hybridNCs (MnMo6@CSIm NCs).The best resulting NCs were evaluated for their anticancer activity against breast cancer cell lines (MCF-7 & MDA-MB-231) as well as HUVEC normal cells using MTT assay. Furthermore, cellular uptake, apoptosis ratio and cell migration inhibition were evaluated on the MDA-MB-231 cell line as the triple-negative aggressive cell line.The optimized NPs had a zeta potential above +27 mV with a uniform distribution of sizes around 145 nm. The loading content and release efficiency were both satisfying (about 44% and 98%). In the release study, a pH-responsive release was detectedcomparing the neutral conditions.The NCs had a better anticancer activity than free MnMo6 in both cancer cell lines, without detectable cytotoxicity against HUVEC normal cells. The cellular uptake was about 100 %, and apoptosis value was enough high (81%) compared to free MnMo6. Interestingly, the MnMo6 hybrid NCs inhibitedthe cell migration of MDA-MB-231 cell line1.5 times better than the free MnMo6. All of these results are fascinating to follow more pre-clinical studies on this hybrid NC.

Background Triple-negative breast cancer (TNBC) is known to have a poor prognosis with limited treatment options. In-house data revealed that miR-214 was up-regulated in breast cancer tissue, but there have been conflicting results about the role of miR-214 in oncogenesis in breast cancer. In this study, we aimed to investigate the potential role of miR-214 and its target in carcinogenesis.Methods We used three breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468) and control breast epithelial cell line (MCF-10A) to evaluate miR-214 expression and function. Target genes were predicted based on pre-formed miRNA databases. miR-214 was transfected into cell lines, and cell proliferation, invasion and migration assays, and RT-PCR analysis were performed. Results MiR-214 was significantly overexpressed in MDA-MB-231 line, which represents TNBC. Fyn-related kinase (FRK) was selected as a potential target of miR-214. Endogenous FRK levels were down-regulated in MDA-MB-231 cells. miR-214 transfected MDA-MB-231 cell line resulted in increased cell proliferation, and silencing FRK using si-FRK also induced cell proliferation in MDA-MB-231 cells. When MDA-MB-231 cells were transfected with miR-214, cell invasion and migration were enhanced. Furthermore, si-FRK-transfected MDA-MB-231 cells showed increased cell invasion and migration compared to the control cells. Conclusions Our results suggest that miR-214 might play a role in tumor proliferation and invasion to promote breast cancer oncogenesis by suppressing FRK activity, leading to cancer progression.

Purpose: HIF-1α has critical roles in formation of Tumor microenvironment by regulating genes involved in angiogenesis and anaerobic respiration. TME fuels tumors growth and metastasis and presents therapy with several challenges. Therefore, we aimed to investigate if Melittin disrupts HIF-1α signaling pathway in breast adenocarcinoma cell line MDA-MB-231.Methods: breast adenocarcinoma cell line MDA-MB-231 was cultured in presence of different doses of Melittin and MTT assay was carried out to measure Melittin’s cytotoxic. Cells were exposed to 5% C2 to mimic hypoxic conditions and Melittin. Western blot was used to measure HIF-1α protein levels. Gene expression analysis was performed using real-time PCR to measure relative mRNA abundance of genes involved in tumor microenvironment formation.Findings: Our results revealed that Melittin effectively inhibits HIF-1α at transcriptional and translation/post-translational level. HIF-1α protein and mRNA level was significantly decreased in Melittin-treated groups. It is found that inhibition of HIF-1α by Melittin is through downregulation of NFκB gene expression. Furthermore, gene expression analysis showed a downregulation in VEGFA and LDHA expression due to inhibition of HIF-1α protein by Melittin. In addition, cell toxicity assay showed that Melittin inhibits the growth of MDA-MB-231 cell line through activation of extrinsic and intrinsic apoptotic pathways by upregulating TNF and BAX expression. Conclusions: Melittin suppresses the expression of genes responsible for formation of TME physiological hallmarks by suppressing HIF-1α signaling pathway. Our results suggest that Melittin can modulate tumor microenvironment by inhibition of VEGFA and LDHA.

Background Ursolic acid (UA), a plant extract from traditional Chinese medicines as well as edible vegetables, exhibits a potent anticancer activity in various tumor cells. Annexin A1(AnxA1) is dysregulated and play a pivotal role in various tumor. However, the function of AnxA1 in breast cancer(BC) remains unclear. Methods Western blot, real-time quantitative polymerase chain reaction(qRT- PCR), transwell, wound healing and immunofluorescence were used to study the biological features of AnxA1 in breast cancer. The stemness of cancer cells was assessed by sphere formation assay. CCK-8 and flow cytometry assay were used to detect the effects of ursolic acid on the growth, proliferation and apoptosis of breast cancer cells in vitro. A nude mice xenograft model was employed in vivo. The potential mechanism by which Ursolic acid regulates the biological behaviors of breast cancer stem cells through AnxA1 via the wnt/β-catenin signaling pathway was tested by western blot, qRT- PCR and immunohistochemistry. Results AnxA1 was highly expressed in MDA-MB-231 cell line compared with MCF-7 cell line, Down-regulation of AnxA1 could reduce the mammosphere formation, inhibit EMT, decrease the ability of migration and invasion in MCF-7 and MDA-MB-231 cells. Ursolic acid can reduce the expression of AnxA1 and inhibit proliferation of breast cancer cells, stemness, EMT, migration and invasion, promote cell apoptosis of breast cancer cell. This studies suggest that the anticancer effects of AnxA1 knockdown and UA treatment may be realized by affecting the EMT process and the wnt/β-catenin signaling pathway. Conclusions This research suggest that AnxA1 knockdown enhanced the sensitivity of breast cancer cells to UA, the combination of UA treatment and AnxA1 knockdown possesses multiple anti-tumor activities against breast cancer, as it, in particular, inhibited the cancer stem cell and attenuated EMT. Therefore, it is emerging as a promising therapeutic strategy to inhibit breast cancer.

Series of catanionic based alkyltrimethylammonium-alkylcarboxylate surfactants systems having different degree of alkyl chain length asymmetry were prepared and tested for their cytotoxicity against both fibroblast 3T3 and breast cancer MDA-MB-231 cell lines. Catanionic surfactant with the highest alkyl chain length possessed significant potent cytotoxicity, with a half maximal inhibitory concentration (IC50) of 4.04 ± 0.06 μM on MDA-MB-231 cell line. Combination of anti-cancer agent (tocotrienol rich fraction,TRF; and curcumin, respectively)with the catanionic at different weight ratios was found to exert lower cytotoxicity on both cell lines as compared to the treated cells with catanionic only. Noticeably, combination of TRF withcatanionic showed higher anti-cancer activities than the incorporation of curcumin with catanionic (resulted low IC50 value). Combination index (CI) of both anti-cancer agent (TRF and curcumin) and catanionic mixtures indicated antagonistic effect (more than 1), respectively, which may explained catanionic surfactant having long alkyl chain length has the potential to act as anti-cancer agent in its pristine form and less effective with other anti-cancer agents combination.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy lack of sensitivity to chemo-, endocrine and targeted therapy. CDK4/6 inhibitors, combined with endocrine therapy, have been proven to be effective in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. So we investigated that whether CDK4/6 inhibitor palbociclib (PD) could enhance effects of cisplatin (CDDP) on TNBC.Methods: The effects of different drug regimens of PD and CDDP on MDA-MB-231 and RB-knockdown MDA-MB-231 (sh-MDA-MB-231) cells were assessed in vitro and vivo. MDA-MB-468 and RB-overexpression MDA-MB-468 cells were used to assess the effect of PD-CDDP regimen in vitro. Immunoblotting illustrated cyclin D1/RB/E2F axis signaling pathway.Results: PD induced G1 phase cell cycle arrest in MDA-MB-231 cell line. However, synchronous treatment with PD and CDDP for 24h, PD used for 24h and then followed by CDDP or CDDP used for 24h and then followed by PD all had no influence on cell apoptosis of MDA-MB-231 cells. We further investigated the effect of PD or CDDP withdrawal on sequential treatment and found that PD used for 48h and then withdrawn for 48h followed by CDDP (PD-CDDP) could significantly increase apoptosis, inhibit cell viability and colony formation of MDA-MB-231 cells, while in other regimens PD and CDDP represented additive or antagonistic response. Preferential use of PD could increase DNA damage by CDDP as measured through γH2AX. These findings above were negative in sh-MDA-MB-231 cells and cell function experiments of MDA-MB-468 and RB-overexpression MDA-MB-468 cells could draw similar conclusions, which indicated that PD enhanced the sensitivity of TNBC cells to CDDP in a RB dependent manner. In vivo, this combination treatment inhibited tumor growth and Ki-67 expression compared with single drug treatments in MDA-MB-231 xenograft models. Western blotting analysis presented that PD enhanced sensitivity to CDDP through CDK4/6-cyclin D-RB-E2F pathway. Conclusions: Pre-treatment with PD synchronized tumor cell cycle through CDK4/6-cyclin D1-RB-E2F pathway, which could increase anti-tumor effect of CDDP. PD-CDDP might be an effective treatment for RB-proficient TNBC patients.