SKBR3 Breast Cancer Cells Research Articles

The complex social ecosystem regulates the spectrum of human behavior. However, it becomes relatively easier to understand if we disintegrate the contributing factors, such as locality and interacting partners. Interestingly, it draws remarkable similarity with the behavior of a residue placed in a social setup of functional groups in a protein. Can it inspire principles for creating a unique environment for the precision engineering of proteins? We demonstrate that localization-regulated interacting partner(s) could render precise and traceless single-site modification of structurally diverse native proteins. The method targets a combination of high-frequency Lys residues through an array of reversible and irreversible reactions. However, excellent simultaneous control over chemoselectivity, site selectivity, and modularity ensures that the user-friendly protocol renders acyl group installation, including post-translational modifications (PTMs), on a single Lys. Besides, it offers a chemically orthogonal handle for the installation of probes. Also, a purification protocol integration delivers analytically pure single-site tagged protein bioconjugates. The precise labeling of a surface Lys residue ensures that the structure and enzymatic activities remain conserved post-bioconjugation. For example, the precise modification of insulin does not affect its uptake and downstream signaling pathway. Further, the method enables the synthesis of homogeneous antibody-fluorophore and antibody-drug conjugates (AFC and ADC; K183 and K249 labeling). The trastuzumab-rhodamine B conjugate displays excellent serum stability along with antigen-specific cellular imaging. Further, the trastuzumab-emtansine conjugate offers highly specific antiproliferative activity toward HER-2 positive SKBR-3 breast cancer cells. This work validates that disintegrate theory can create a comprehensive platform to enrich the chemical toolbox to meet the technological demands at the chemistry, biology, and medicine interface.

The aim of this study was to make de novo gold nanoparticles (Au(0)NPs) that turn on p53 and turn off NF-kB signaling in SKBR3 breast cancer cells. The chemical method was used to make the erythromycin-based Au(0)NPs. Authentic techniques were used to figure out what these Au(0)NPs were like. In the end, relative gene expression studies were used to treat SKBR3 breast cancer cells with these Au(0)NPs as a nanomedicine. When Au(0)NPs were present, the levels of caspases 3, 8, and 9 changed, p53 was turned on, and NF-kB was turned off at the same time. Compared to normal breast cells, the number of breast cancer cells (SKBR3) that could live was cut down (CRL-4010). Gene expressions of caspases also showed that the data were correct. When AuNPs were used to treat breast cancer cells, it was found that p53 and NF-kB had the opposite relationship. The study laid out a first step for using newly made AuNPs as a chemotherapeutic agent to treat SKBR3 cells.

The expression of myoglobin (MB), well known as the oxygen storage and transport protein of myocytes, is a novel hallmark of the luminal subtype in breast cancer patients and correlates with better prognosis. The mechanisms by which MB impacts mammary tumorigenesis are hitherto unclear. We aimed to unravel this role by using CRISPR/Cas9 technology to generate MB-deficient clones of MCF7 and SKBR3 breast cancer cell lines and subsequently characterize them by transcriptomics plus molecular and functional analyses. As main findings, loss of MB at normoxia upregulated the expression of cell cyclins and increased cell survival, while it prevented apoptosis in MCF7 cells. Additionally, MB-deficient cells were less sensitive to doxorubicin but not ionizing radiation. Under hypoxia, the loss of MB enhanced the partial epithelial to mesenchymal transition, thus, augmenting the migratory and invasive behavior of cells. Notably, in human invasive mammary ductal carcinoma tissues, MB and apoptotic marker levels were positively correlated. In addition, MB protein expression in invasive ductal carcinomas was associated with a positive prognostic value, independent of the known tumor suppressor p53. In conclusion, we provide multiple lines of evidence that endogenous MB in cancer cells by itself exerts novel tumor-suppressive roles through which it can reduce cancer malignancy.

Objectives: Given the need to establish less invasive treatments that improve the patient’s quality of life and still have antitumour effects, this study aimed to evaluate the behaviour of breast cancer tumour cells (SKBR3 and PMC42) by treatment with ultradiluted Ruta graveolens (Ruta D35). Material and Methods: The breast cancer cell lines SKBR3 and PMC42 were treated with ultradiluted Ruta D35 and the in vitro effects on cell viability was evaluated by MTT cytotoxicity assay. Results: In the SKBR3 cells, Ruta D35 at concentration of 8 μl/ml induced a significant reduction in cell viability when compared to the untreated control. The treatment with Ruta D35 in the PMC42 cells reduced cell viability from the treatment at the highest concentrations of 20 μl/ml, 30 μl/ml, 40 μl/ml and 50 μl/ml. Conclusion: Ruta D35 presented in vitro cytotoxic activity in SKBR3 and PMC42 breast cancer cells, thereby reducing cell viability. However, further tests are necessary to better understand the cytotoxic action and the potential of R. graveolens for treating breast tumour cells.

IntroductionBreast cancer is among the most prevalent type of cancer in women across the world. The essential oils of Pistacia atlantica Desf. have been utilized as a medicine owing to their antibacterial, antioxidant, anti-inflammatory, and anticancer effects. The current research aims to enhance the anticancer effect of the essential oil of Pistacia atlantica Desf. by incorporating it in a nanostructured lipid carrier (NLC), a lipid-based drug delivery system. MethodsNLCs-containing Pistacia atlantica Desf. essential oil was prepared by probe ultrasonication method to obtain Pistacia atlantica Desf. EO-loaded NLCs (PAEO-NLCs) and its anticancer effect against SKBR3 breast cancer cells was investigated. Dynamic light scattering (DLS) method was used to determine the particle size, as well as polydispersity index (PDI) and zeta potential (ZP) of formulations. Transmission electron microscopy (TEM) was also used to determine the size and morphology of optimized formulation (PAEO-NLC4). In vitro cellular assays (MTT, apoptosis, and cell cycle) were employed to assess the anticancer effect of PAEO-NLC4 against SKBR3 cells. ResultsTEM results revealed that PAEO-NLC4 have a well-defined spherical shape, with a size of 151 ± 1 nm, with a negative surface charge of − 29.1 ± 1.4 mV, and a PDI of 0.16 ± 0.03. Cellular data revealed that the PAEO-NLC4 can decline the viability of SKBR3 cells through cell cycle arrest and apoptosis, compared to cells treated with placebo and free PAEO. ConclusionsBased on our findings, PAEO-NLC4 could serve as a potential and effective treatment for breast cancer therapy.

Simple SummaryATPase family AAA domain-containing protein 2 (ATAD2) overexpression is associated with poor survival and disease recurrence in multiple cancers. The current study aimed to investigate the expression and function of ATAD2 in breast cancer. Our results showed that ATAD2 expression was upregulated in human breast cancer tissues and cell lines, while ATAD2 knockdown inhibited the proliferation, migration, and invasion of breast cancer cells. Moreover, we provide evidence suggesting that miR-302 directly targets ATAD2 and thus modulates cancer cell proliferation, migration, and invasion in vitro. Moreover, ATAD2 overexpression rescued the inhibition of tumor growth caused by miR-302 in xenograft mice. These findings indicate that miR-302 plays a crucial role in inhibiting the malignant phenotypes of breast cancer cells by targeting ATAD2.Breast cancer is the most common malignant tumor in women. The ATPase family AAA domain-containing protein 2 (ATAD2) contains an ATPase domain and a bromodomain, and is abnormally expressed in various human cancers, including breast cancer. However, the molecular mechanisms underlying the regulation of ATAD2 expression in breast cancer remain unclear. This study aimed to investigate the expression and function of ATAD2 in breast cancer. We found that ATAD2 was highly expressed in human breast cancer tissues and cell lines. ATAD2 depletion via RNA interference inhibited the proliferation, migration, and invasive ability of the SKBR3 and T47D breast cancer cell lines. Furthermore, Western blot analysis and luciferase assay results revealed that ATAD2 is a putative target of miR-302. Transfection with miR-302 mimics markedly reduced cell migration and invasion. These inhibitory effects of miR-302 were restored by ATAD2 overexpression. Moreover, miR-302 overexpression in SKBR3 and T47D cells suppressed tumor growth in the xenograft mouse model. However, ATAD2 overexpression rescued the decreased tumor growth seen after miR-302 overexpression. Our findings indicate that miR-302 plays a prominent role in inhibiting the cancer cell behavior associated with tumor progression by targeting ATAD2, and could thus be a valuable target for breast cancer therapy.

Antiproliferative Potential of Bacillus coagulans Supernatant on SKBR3 Breast Cancer Cell Line

Background: Breast cancer is the most lethal cancer causing death among women, especially in developed countries. Using medicinal plants and natural resources to control and prevent different types of cancer in human has been the focus of attention. Objectives: The current study aimed to investigate the possible effects of hydroalcoholic extracts from some plant species such as Lavandula angustifolia, Ephedra major, and Scenedesmus obliquus on cell viability of two breast cancer MCF7 and SK-BR3 cell lines. Methods: MTT assay and gene expression analysis were performed adopting qRT-PCR method. Target cells were treated with different concentrations of plant extracts in a 24-hour period. Data were analyzed using Graphpad Prism version 8.3.0. Differences among means were determined using Student’s t-test or one-way ANOVA with Dunnett’s Multiple Comparison Test. Results: An indirect relationship was detected between extract concentration and cell viability. The result of the cell viability (IC-50) showed that the extract of S. obliquus had the maximum effect on both tested cells at concentrations above 100 µg/mL. A high cell death rate was observed in MCF-7 cell line compared to SK-BR3 cell line 24 h after the treatment. According to results from gene expression analysis, Caspase 3 gene increased in all treated cells, while the bcl-xl gene expression declined in the tested cells. Conclusions: It was concluded that the extracts from three plants had both positive and dose-related effects on MCF-7 and SK-BR3 cell line. However, it was recommended that future complementary studies should be conducted in order to evaluate the cell viability effect of these plants on human cancer.

DDT and its metabolites (DDTs) can induce estrogenic effects. Previous mechanistic investigations mainly concentrated on activating the genomic transcription of estrogen receptor (ER) pathways. Here, we identified whether estrogen-related receptor γ (ERRγ), an orphan nuclear receptor, is a potential target of DDTs by receptor binding, transcriptional activity, and receptor-mediated pathway assays. Fluorescence polarization-based binding assays showed that all eight DDTs bound to ERRγ directly, with Kd values ranging from 0.73-168.82 μM. Among them, 2,2-bis(4-chlorophenyl)ethanol (4,4'-DDOH) exhibited the highest binding affinity, which was 2.5-fold stronger than GSK4716, a well-known ERRγ agonist. Eight DDTs exhibited agonistic activity toward the ERRγ pathway, with 4,4'-DDOH showing the strongest potency. In silico studies revealed that DDTs tended to bind with ERRγ in the agonistic conformation. Using a SKBR3 breast cancer cell model, we further found that nanomolar or micromolar levels of DDTs significantly activated the ERRγ pathway in cells and induced cell proliferation through the ERRγ-modulated cell cycle. These results indicated that the binding and activation of DDTs to ERRγ might serve as molecular initiating events for subsequent ERRγ-mediated signaling pathways and adverse outcomes. Overall, our results demonstrated that ERRγ might be a crucial pathway involved in the estrogenic disruption effects of DDTs.

A unique series of 6, 7-disubstituted 7H-purine analogues were designed with the goal of developing potential EGFR/HER2 dual tyrosine kinase inhibitors to treat human breast cancers. The compounds were rationally developed by replacing the central quinazoline core of lapatinib, an established drug that suppresses both EGFR and HER2, another essential member of this receptor family. Twelve compounds were synthesized by substituting hydrophilic '6-(3-chloro-4-[(substituted pyridin-3-yl) oxy]) anilino' group at 6th position and '(3E)-5-(dimethylamino) pent-3-en-2-ol' side chain at 7th position of purine scaffold which was thought to be considered critical for dual EGFR/HER2 inhibition. The chemical structures of the synthesized compounds were confirmed by 1H, 13C NMR, and HRMS analysis. All these compounds were evaluated for EGFR family tyrosine kinase (EGFR, HER2, HER3, and HER4) in-vitro inhibition. The results showed compound 8e as a potent dual EGFR/HER2 inhibitor with IC50 values of 0.021 ± 0.007 µM (EGFR) and 0.019 ± 0.009 µM (HER2), respectively, which were comparable to lapatinib (EGFR: 0.019 ± 0.007; HER2: 0.016 ± 0.003 µM), a positive control. EGFR/HER2 phosphorylation inhibition studies proved potential for 8e in dual kinase inhibition. In support of the dual inhibitory activity against both EGFR and HER2, compound 8e exhibited potent cytotoxic activity against BT-474 and SKBR3 cells, with IC50 values of 2.26 ± 0.37 µM (BT-474) and 2.17 ± 0.45 µM (SKBR3), which was comparable to the standard Lapatinib (EGFR: 2.63 ± 0.45 µM; HER2: 1.84 ± 0.39 µM). Additionally, compound 8e caused significant G2/M phase cell cycle arrest, resulting in a fivefold increase in cell number compared to control SKBR3 cells, and potentially induced apoptosis in 79% of these cells, which was comparable to that of lapatinib (83%). These new findings could provide an important basis for further developing compound 8e as a potent EGFR/HER2 dual kinase inhibitor.

Electrochemical techniques offer great opportunities for the capture of chemical and biological entities from complex mixtures and their subsequent release into clean buffers for analysis. Such methods are clean, robust, rapid, and compatible with a wide range of biological fluids. Here, we designed an electrochemically addressable system, based on a conducting terpolymer [P(EDOT-co-EDOTSAc-co-EDOTEG)] coated onto a carbon cloth substrate, to selectively capture and release biological entities using a simple electrochemical redox process. The conducting terpolymer composition was optimized and the terpolymer-coated carbon cloth was extensively characterized using electrochemical analysis, Raman and Fourier transform-infrared spectroscopy, water contact angle analysis, and scanning electron microscopy. The conductive terpolymer possesses a derivative of EDOT with an acetylthiomethyl moiety (EDOTSAc), which is converted into a "free" thiol that then undergoes reversible oxidation/reduction cycles at +1.0 V and -0.8 V (vs Ag/AgCl), respectively. That redox process enables electrochemical capture and on-demand release. We first demonstrated the successful electrochemical capture/release of a fluorescently labeled IgG antibody. The same capture/release procedure was then applied to release extracellular vesicles (EVs), originating from both MCF7 and SKBR3 breast cancer cell line bioreactors. EVs were captured using the substrate-conjugated HER2 antibody which was purified from commercially available trastuzumab. Capture and release of breast cancer EVs using a trastuzumab-derived HER2 antibody has not been reported before (to the best of our knowledge). A rapid (2 min) release at a low potential (-0.8 V) achieved a high release efficiency (>70%) of the captured, HER2+ve, SKBR3 EVs. The developed system and the electrochemical method are efficient and straightforward and have vast potential for the isolation and concentration of various biological targets from large volumes of biological and other (e.g., environmental) samples.

Copine 1 (CPNE1) is a calciumdependent phospholipid protein that has been shown to regulate the AKT serine/threonine kinase 1 (AKT) signaling pathway to mediate its function in various cell types. However, little is known about the physiological function of this protein in breast cancer cells. We aimed to investigate the prognostic and therapeutic value of CPNE1 in erb-b2 receptor tyrosine kinase 2 [human epidermal growth factor receptor 2 (HER2)]-positive and luminal A subtypes of breast cancer. Western blotting, cell viability, wound-healing and invasion assays were performed on SK-BR3 and MCF-7 breast cancer cells with forced overexpression of CPNE1. CPNE1 immunohistochemical (IHC) staining and bioinformatics analysis were performed on specimens from patients with breast cancer and compared to normal breast samples. CPNE1 overexpression promoted AKT activation, and increased cell viability and cell motility in SK-BR3 and MCF-7 breast cancer cells. In addition, invasive capabilities of SK-BR3 cells were increased by the overexpression of CPNE1. The expression levels of CPNE1 were higher in HER2-positive and luminal A subtypes of human breast cancer tissues compared with those in adjacent normal tissues. Furthermore, CPNE1 expression was increased in RNA microarray analysis of samples from patients with breast cancer compared to normal breast samples. CPNE1 may play a key role in the pathophysiology of HER2-positive and luminal A subtypes of breast cancer.

BackgroundTriple negative breast cancer (TNBC) is an aggressive disease characterized by high risk of relapse and development of resistance to different chemotherapy agents. Several targeted therapies have been investigated in TNBC with modest results in clinical trials. Among these, PI3K/AKT inhibitors have been evaluated in addition to standard therapies, yielding conflicting results and making attempts on elucidating inherent mechanisms of resistance of great interest. Increasing evidences suggest that PI3K/AKT inhibitors can induce autophagy in different cancers. Autophagy represents a supposed mechanism of drug-resistance in aggressive tumors, like TNBC. We, therefore, investigated if two PI3K/AKT inhibitors, ipatasertib and taselisib, could induce autophagy in breast cancer models, and whether chloroquine (CQ), a well known autophagy inhibitor, could potentiate ipatasertib and taselisib anti-cancer effect in combination with conventional chemotherapy.MethodsThe induction of autophagy after ipatasertib and taselisib treatment was evaluated in MDAMB231, MDAM468, MCF7, SKBR3 and MDAB361 breast cancer cell lines by assaying LC3-I conversion to LC3-II through immunoblotting and immunofluorescence. Other autophagy-markers as p62/SQSTM1 and ATG5 were evaluated by immunoblotting. Synergistic antiproliferative effect of double and triple combinations of ipatasertib/taselisib plus CQ and/or paclitaxel were evaluated by SRB assay and clonogenic assay. Anti-apoptotic effect of double combination of ipatasertib/taselisib plus CQ was evaluated by increased cleaved-PARP by immunoblot and by Annexin V- flow cytometric analysis. In vivo experiments were performed on xenograft model of MDAMB231 in NOD/SCID mice.ResultsOur results suggested that ipatasertib and taselisib induce increased autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiates the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy.ConclusionThese data suggest that inhibition of authophagy with CQ could overcome mechanism of drug resistance to PI3K/AKT inhibitors plus paclitaxel in TNBC making the evaluation of such combinations in clinical trials warranted.

The development of peptide inhibitors against intracellular targets depends upon the dual challenge of achieving a high affinity and specificity for the target and maintaining cellular permeability for biological activity. Previous efforts to develop bicyclic peptides targeted to the Grb7 signalling protein implicated in HER2+ve cancer progression have resulted in improved affinity. However, these same peptides demonstrated a lowered activity due to their decreased ability to penetrate cell membranes. Here, we report the testing of a new series of bicyclic G7 peptides designed to possess improved bioactivity. We discovered that the incorporation of two amino acids (Phe-Pro, Phe-Trp or Phe-Arg) within the bicyclic peptide framework maintains an enhanced binding affinity for the Grb7-SH2 domain compared to that of the first-generation monocyclic peptide G7-18NATE. Structure determination using X-ray crystallography revealed that the mode of binding by the expanded bicyclic G7 peptide is analogous to that of G7-18NATE. Interestingly, while the bicyclic peptide containing Phe-Trp did not display the highest affinity for Grb7-SH2 in the series, it was the most potent inhibitor of HER2+ve SKBR3 breast cancer cell migration when coupled to Penetratin. Together, this demonstrates that peptide flexibility as well as the amino acid tryptophan can play important roles in the uptake of peptides into the cell.

Shahin Aghamiri, Ali Jafarpour, Mohsen Shoja: ‘Effects of silver nanoparticles coated with anti‐HER2 on irradiation efficiency of SKBR3 breast cancer cells’, IET Nanobiotechnology, 2019, 13, (8), pp. 808‐815. (https://ietresearch.onlinelibrary.wiley.com/doi/10.1049/iet‐nbt.2018.5258).The above article, published online on 19 August 2019 in Wiley Online Library (ietresearch.onlinelibrary.wiley.com), has been retracted by agreement between the journal Editor in Chief Ronald Pethig, the Institution of Engineering and Technology, and John Wiley and Sons Ltd. The retraction has been agreed because none of the listed authors ‐ Mohsen Shoja, Ali Jafarpour and Shahin Aghamiri ‐ fulfil the journal's criteria for authorship for the research published in the article. The article was submitted for publication by Mohsen Shoja without the consent of the legitimate authors or attribution to the legitimate authors.

Characterization and optimization of co-delivery Farnesol-Gingerol Niosomal formulation to enhance anticancer activities against breast cancer cells

Nanosized materials have been proposed for a wide range of biomedical applications, given their unique characteristics. However, how these nanomaterials interact with cells and tissues, as well as how they bio-distribute in organisms, is still under investigation. Differences such as the nanoparticle size, shape, and surface chemistry affect the basic mechanisms of cellular uptake and responses, which, in turn, affects the nanoparticles’ applicability for biomedical applications. Thus, it is vital to determine how a specific nanoparticle interacts with cells of interest before extensive in vivo applications are performed. Here, we delineate the uptake mechanism and localization of gold nanorods in SKBR-3 and MCF-7 breast cancer cell lines. Our results show both differences and similarities in the nanorod–cell interactions of the two cell lines. We accurately quantified the cellular uptake of gold nanorods in SKBR-3 and MCF-7 using inductively coupled plasma mass spectrometry (ICP-MS). We found that both cell types use macropinocytosis to internalize bare nanorods that aggregate and associate with the cell membrane. In addition, we were able to qualitatively track and show intracellular nanoparticle localization using transmission electron microscopy. The results of this study will be invaluable for the successful development of novel and “smart” nanodrugs based on gold nano-structural delivery vehicles, which heavily depend on their complex interactions with single cells.

Combination chemotherapy has become a treatment modality for breast cancer. However, serious side effects and high cytotoxicity associated with this combination therapy make it a high-risk method for breast cancer treatment. This study evaluated the anticancer effect of decorated niosomal nanocarriers loaded with cisplatin (CIS) and epirubicin (EPI) in vitro (on SKBR3 and 4T1 breast cancer cells) and in vivo on BALB/c mice. For this purpose, polyethylene glycol (PEG) and folic acid (FA) were employed to prepare a functionalized niosomal system to improve endocytosis. FA-PEGylated niosomes exhibited desired encapsulation efficiencies of ∼91.2 and 71.9% for CIS and EPI, respectively. Moreover, cellular assays disclosed that a CIS and EPI-loaded niosome (NCE) and FA-PEGylated niosomal CIS and EPI (FPNCE) enhanced the apoptosis rate and cell migration in SKBR3 and 4T1 cells compared to CIS, EPI, and their combination (CIS+EPI). For FPNCE and NCE groups, the expression levels of Bax, Caspase3, Caspase9, and Mfn1 genes increased, whereas the expression of Bcl2, Drp1, MMP-2, and MMP-9 genes was downregulated. Histopathology results showed a reduction in the mitosis index, invasion, and pleomorphism in BALB/c inbred mice with NCE and FPNCE treatment. In this paper, for the first time, we report a niosomal nanocarrier functionalized with PEG and FA for codelivery of CIS and EPI to treat breast cancer. The results demonstrated that the codelivery of CIS and EPI through FA-PEGylated niosomes holds great potential for breast cancer treatment.

(1) Background: In oncology research, a long-standing discussion exists about pros and cons of metal nanoparticle-enhanced radiotherapy and real mechanisms behind the tumor cell response to irradiation (IR) in presence of gold nanoparticles (GNPs). A better understanding of this response is, however, necessary to develop more efficient and safety nanoparticle (NP) types designed to disturb specific processes in tumor cells. (2) Aims and Methods: We combined 3D confocal microscopy and super-resolution single molecule localization microscopy (SMLM) to analyze, at the multiscale, the early and late effects of 10 nm-GNPs on DNA double strand break (DSB) induction and repair in tumor cells exposed to different doses of photonic low-LET (linear energy transfer) radiation. The results were correlated to different aspects of short and long-term cell viability. SkBr3 breast cancer cells (selected for the highest incidence of this cancer type among all cancers in women, and because most breast tumors are treated with IR) were incubated with low concentrations of GNPs and irradiated with 60Co γ-rays or 6 MV X-rays. In numerous post-irradiation (PI) times, ranging from 0.5 to 24 h PI, the cells were spatially (3D) fixed and labeled with specific antibodies against γH2AX, 53BP1 and H3K9me3. The extent of DSB induction, multi-parametric micro- and nano-morphology of γH2AX and 53BP1 repair foci, DSB repair kinetics, persistence of unrepaired DSBs, nanoscale clustering of γH2AX and nanoscale (hetero)chromatin re-organization were measured by means of the mentioned microscopy techniques in dependence of radiation dose and GNP concentration. (3) Results: The number of γH2AX/53BP1 signals increased after IR and an additional increase was observed in GNP-treated (GNP(+)) cells compared to untreated controls. However, this phenomenon reflected slight expansion of the G2-phase cell subpopulation in irradiated GNP(+) specimens instead of enhanced DNA damage induction by GNPs. This statement is further supported by some micro- and nano-morphological parameters of γH2AX/53BP1 foci, which slightly differed for cells irradiated in absence or presence of GNPs. At the nanoscale, Ripley’s distance frequency analysis of SMLM signal coordinate matrices also revealed relaxation of heterochromatin (H3K9me3) clusters upon IR. These changes were more prominent in presence of GNPs. The slight expansion of radiosensitive G2 cells correlated with mostly insignificant but systematic decrease in post-irradiation survival of GNP(+) cells. Interestingly, low GNP concentrations accelerated DSB repair kinetics; however, the numbers of persistent γH2AX/53BP1 repair foci were slightly increased in GNP(+) cells. (4) Conclusions: Low concentrations of 10-nm GNPs enhanced the G2/M cell cycle arrest and the proportion of radiosensitive G2 cells, but not the extent of DNA damage induction. GNPs also accelerated DSB repair kinetics and slightly increased presence of unrepaired γH2AX/53BP1 foci at 24 h PI. GNP-mediated cell effects correlated with slight radiosensitization of GNP(+) specimens, significant only for the highest radiation dose tested (4 Gy).

Platinum complexes inhibit HER-2 enriched and triple-negative breast cancer cells metabolism to suppress growth, stemness and migration by targeting PKM/LDHA and CCND1/BCL2/ATG3 signaling pathways.