MCF-7 Human Breast Cancer Cells Research Articles

Biogenic polymer-encapsulated diosgenin nanoparticles: Biodistribution, pharmacokinetics, cellular internalization, and anticancer potential in breast cancer cells and tumor xenograft

Diosgenin (DGN) is a natural bioactive steroidal saponin from therapeutic herbs and it exhibits potential anticancer efficacy. Here, we report the preparation of poly lactide-co-glycolide (PLGA)-encapsulated diosgenin nanoparticles (PLGA-DGN NPs) and characterization of their physicochemical nature, and morphology as well as inspect their drug-loading capability, in vitro drug release, pharmacokinetics, bio-distribution, safety profile. The in vitro and in vivo antineoplastic activities of PLGA-DGN NPs were also examined against the MCF-7 breast cancer cell line and in the Ehrlich ascites carcinoma (EAC) tumor xenograft model, respectively. The results displayed an appropriate size (∼147 nm), spherical shape, and a narrow polydispersity index. The nanoparticles showed a high encapsulation efficacy (78%), loading capacity (8%), good colloidal stability, and an initial burst release at an acidic medium. The nanoparticles exhibited significant cytotoxic activity at their IC50 dose compared to diosgenin. PLGA-DGN NPs facilitated cellular internalization of DGN in human breast cancer MCF-7 cells and extended the blood circulation time showing an excellent pharmacokinetic profile. Bio-distribution study revealed that PLGA-DGN NPs could significantly enhance DGN accumulation in tumor tissue. The safety profile of the PLGA-DGN NPs was confirmed in histopathologic, hematologic, and immunologic parameters of Swiss albino mice. At the same time, an effective antiangiogenic, and antiproliferative potential of PLGA-DGN NPs were exhibited in mice tumor xenograft model by showing tumor regression and down-regulating CD31 and Ki-67 expression. Therefore, PLGA-DGN NPs could be utilized as a promising anticancer drug, opening up a new avenue for further research.

(-)-Xanthatin as a Killer of Human Breast Cancer MCF-7 Mammosphere Cells: A Comparative Study with Salinomycin.

Experimental evidence accumulated by our research group and others strongly suggests that (–)-xanthatin, a xanthanolide sesquiterpene lactone, exhibits anti-proliferative effects on human breast cancer cells (in vitro) as well as anti-tumor effects in experimental animals (in vivo). In cancer biology, it is now critically important for anti-cancer agents to selectively target cancer stem cells (CSCs) in order to overcome cancer therapeutic resistance and recurrence. However, it has not yet been established whether (–)-xanthatin abrogates the formation of breast CSCs. In the present study, we utilized chemically synthesized pure (–)-xanthatin and a culture system to obtain mammospheres from human breast cancer MCF-7 cells, which are a CSC-enriched population. We herein demonstrated for the first time that (–)-xanthatin exhibited the ability to kill mammospheres, similar to salinomycin, an established selective killer of CSCs. A possible anti-proliferative mechanism toward mammospheres by (–)-xanthatin is discussed.

Synthesis, Characterisation and Mechanism of Action of Anticancer 3-Fluoroazetidin-2-ones.

The stilbene combretastatin A-4 (CA-4) is a potent microtubule-disrupting agent interacting at the colchicine-binding site of tubulin. In the present work, the synthesis, characterisation and mechanism of action of a series of 3-fluoro and 3,3-difluoro substituted β-lactams as analogues of the tubulin-targeting agent CA-4 are described. The synthesis was achieved by a convenient microwave-assisted Reformatsky reaction and is the first report of 3-fluoro and 3,3-difluoro β-lactams as CA-4 analogues. The β-lactam compounds 3-fluoro-4-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxy phenyl)azetidin-2-one 32 and 3-fluoro-4-(3-fluoro-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one) 33 exhibited potent activity in MCF-7 human breast cancer cells with IC50 values of 0.075 µM and 0.095 µM, respectively, and demonstrated low toxicity in non-cancerous cells. Compound 32 also demonstrated significant antiproliferative activity at nanomolar concentrations in the triple-negative breast cancer cell line Hs578T (IC50 0.033 μM), together with potency in the invasive isogenic subclone Hs578Ts(i)8 (IC50 = 0.065 μM), while 33 was also effective in MDA-MB-231 cells (IC50 0.620 μM). Mechanistic studies demonstrated that 33 inhibited tubulin polymerisation, induced apoptosis in MCF-7 cells, and induced a downregulation in the expression of anti-apoptotic Bcl2 and survivin with corresponding upregulation in the expression of pro-apoptotic Bax. In silico studies indicated the interaction of the compounds with the colchicine-binding site, demonstrating the potential for further developing novel cancer therapeutics as microtubule-targeting agents.

Novel estrogen-responsive genes (ERGs) for the evaluation of estrogenic activity.

Estrogen action is mediated by various genes, including estrogen-responsive genes (ERGs). ERGs have been used as reporter-genes and markers for gene expression. Gene expression profiling using a set of ERGs has been used to examine statistically reliable transcriptomic assays such as DNA microarray assays and RNA sequencing (RNA-seq). However, the quality of ERGs has not been extensively examined. Here, we obtained a set of 300 ERGs that were newly identified by six sets of RNA-seq data from estrogen-treated and control human breast cancer MCF-7 cells. The ERGs exhibited statistical stability, which was based on the coefficient of variation (CV) analysis, correlation analysis, and examination of the functional association with estrogen action using database searches. A set of the top 30 genes based on CV ranking were further evaluated quantitatively by RT-PCR and qualitatively by a functional analysis using the GO and KEGG databases and by a mechanistic analysis to classify ERα/β-dependent or ER-independent types of transcriptional regulation. The 30 ERGs were characterized according to (1) the enzymes, such as metabolic enzymes, proteases, and protein kinases, (2) the genes with specific cell functions, such as cell-signaling mediators, tumor-suppressors, and the roles in breast cancer, (3) the association with transcriptional regulation, and (4) estrogen-responsiveness. Therefore, the ERGs identified here represent various cell functions and cell signaling pathways, including estrogen signaling, and thus, may be useful to evaluate estrogenic activity.

A new nanohybrid with BODIPY and Fe3O4 modified graphdiyne oxide in theranostic

Graphdiyne (GDY) is a new 2D carbon material different from graphene, and its ideal drug carrying and photothermal therapy efficacy had been noticed recently. Graphdiyne-oxide (GDYO), which few phototherapy researches had been reported, has more oxygen functional groups than GDY. Metal-organic framework materials Fe3O4@UiO-66-NH2 (FU) can covalently connect to GDYO layers and obtain covalent-organic framework-like structures FUGYO. FU enlarged interlamellar space of GDYO, which avoided the aggregation of FUGYO multiple layers. At the same time, more acetylenic bonds and hydrophilic group were exposed, which brings out advantages like stability, hydrophily, high drug-loading, as well as magnetic targeting and better magnetic resonance imaging efficacy. To promote cancer treatment effect and water solubility, we loaded chemotherapy drug doxorubicin (DOX) in FUGYO, then encapsulated FUGYO/DOX in phosphatidylcholine and fluorescent organic polymer BODIPY-PEG (BP) to integrate image-guided and synergistic therapy in one nanoparticle (BPFG/DOX). Due to the unique structure of BPFG/DOX, the π–π interaction between GDYO and BP improved photodynamic therapy efficiency. About 10 μg ml−1 BPFG/DOX have nearly 90% cell lethality to MCF-7 (human breast cancer cell line) cells with laser irradiation. In vivo, BPFG/DOX possessed ideal magnetic targeting and effectively inhibited tumor growth in 6 d. In conclusion, BPFG/DOX not only acts as an excellent tumor theranostic agent but also provides a scheme for applying GDYO in the biomedical region.

Synthesis and in vitro evaluation of antimycobacterial activity of two palladium(II) complexes based on 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives

In this work, two palladium(II) complexes, namely, [Pd(L1)2(phen)] 1 and [Pd(L2)2(phen)] 2 (L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and phen = 1,10-phenanthroline), were prepared and charactherized by conventional techniques. In both complexes, the spectral data indicated that L1 and L2 are coordinated to the metal in a monodentate manner through the sulfur atom (S−), while a phenanthroline molecule acting as a bidentate ligand completes the coordination sphere. This proposal was supported by DFT calculation of structures and NMR spectra. Subsequently, the free ligands and their metal complexes were tested in vitro against the human prostate cell lines PNT-2 (non-tumorigenic), LNCaP (androgen-sensitive prostate cancer) and PC-3 (castration-resistant prostate cancer), as well as in two human breast cancer cell lines, MCF7 (luminal) and MDA-MB231 (triple-negative). Regarding cytotoxicity, all compounds were considered inactive, since the IC50 values found were higher than 80 µM. The complexes were also evaluated for activity against Mycobacterium tuberculosis, and 1 showed good activity (MIC = 8.94 µg/mL), while 2 exhibited moderate to poor activity (MIC > 25.0 µg/mL), revealing that an increase in the aliphatic chain makes it less active. A conformation sampling was conducted for the complexes 1 and 2 using molecular dynamics simulation. The analysis provided a clear picture of the steric and electrostatic flexibility of these compounds, which is an important feature for multi-target drugs.

Enzyme-triggered- and tumor-targeted delivery with tunable, methacrylated poly(ethylene glycols) and hyaluronic acid hybrid nanogels

Enzyme-responsive polymeric-based nanostructures are potential candidates for serving as key materials in targeted drug delivery carriers. However, the major risk in their prolonged application is fast disassembling of the short-lived polymeric-based structures. Another disadvantage is the limited accessibility of the enzyme to the moieties that are located inside the network. Here, we report on a modified environmentally responsive and enzymatically cleavable nanogel carrier that contains a hybrid network. A properly adjusted volume phase transition (VPT) temperature allowed independent shrinking of a) poly(ethylene glycol) methyl ether methacrylate (OEGMA) with di(ethylene glycol) and b) methyl ether methacrylate (MEO2MA) part of the network, and the exposition of hyaluronic acid methacrylate (MeHa) network based carboxylic groups for its targeted action with the cellular based receptors. This effect was substantial after raising temperature in typical hyperthermia-based treatment therapies. Additionally, novel tunable NGs gained an opportunity to store- and to efficient-enzyme-triggered release relatively low but highly therapeutic doses of doxorubicin (DOX) and mitoxantrone (MTX). The controlled enzymatic degradation of NGs could be enhanced by introducing more hyaluronidase enzyme (HAdase), that is usually overexpressed in cancer environments. MTT assay results revealed effective cytotoxic activity of the NGs against the human MCF-7 breast cancer cells, the A278 ovarian cancer cells and also cytocompatibility against the MCF-10A and HOF healthy cells. The obtained tunable, hybrid network NGs might be used as a useful platform for programmed delivery of other pharmaceuticals and diagnostics in therapeutic applications.

DNA Repair Inhibitors Potentiate Fractionated Radiotherapy More Than Single-Dose Radiotherapy in Breast Cancer Cells.

Simple SummaryDNA damage response (DDR) inhibitors have been shown to sensitize cells to radiation yet have seen limited application in clinical settings. This could be due to a lack of understanding of how these inhibitors interact with ionizing radiation (IR) dose fractionation and cellular repair. Our study investigated the radiosensitizing effect of different DDR inhibitors on human breast cancer cells, utilizing single-dose and fractionated IR. Their effect on damage repair, DNA double-strand break repair kinetics and cell cycle distribution was also evaluated. The main finding was that radiosensitization by DDR inhibition was more prominent when combined with fractionated IR than single-dose IR. Moreover, DDR inhibition impeded the repair of IR-induced DNA double-strand breaks. Altogether, our study established the radiosensitizing potential of DDR inhibitors while highlighting the importance of IR dose fractionation in similar studies.Pharmacological inhibitors of DNA damage response (DDR) proteins, such as the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) kinases and poly (ADP-ribose) polymerase (PARP), have been developed to overcome tumor radioresistance. Despite demonstrating radiosensitization preclinically, they have performed suboptimally in clinical trials, possibly due to an incomplete understanding of the influence of DDR inhibition on ionizing radiation (IR) dose fractionation and sublethal damage repair. Hence, this study aimed to evaluate the radiosensitizing ability under fractionation of ATM inhibitor AZD0156, ATR inhibitor AZD6738 and PARP inhibitor AZD2281 (olaparib), utilizing MDA-MB-231 and MCF-7 human breast cancer cells. Clonogenic assays were performed to assess cell survival and sublethal damage repair after treatment with DDR inhibitors and either single-dose or fractionated IR. Immunofluorescence microscopy was utilized to evaluate DNA double-strand break repair kinetics. Cell cycle distributions were investigated using flow cytometry. All inhibitors showed significant radiosensitization, which was significantly greater following fractionated IR than single-dose IR. They also led to more unrepaired DNA double-strand breaks at 24 h post-IR. This study provides preclinical evidence for the role of AZD0156, AZD6738 and olaparib as radiosensitizing agents. Still, it highlights the need to evaluate these drugs in fractionated settings mirroring clinical practice to optimize the trial design.

Cytotoxic Effects of Rheum khorasanicum Extract on MCF-7 Human Breast Cancer Cell Line and ODC1 Gene Expression

Background: Polyamine metabolism has a critical role in cancer initiation and progression. The abnormal overexpression of the ornithine decarboxylase (ODC1) enzyme gene could be a characteristic of cancer cells. Objectives: The current study evaluated the cytotoxic effects of Rheum khorasanicum extract in three different solvents, including distilled water, ethanol, and n-hexane, on the MCF-7 breast cancer cell line and assessed the expression level of the ODC1 gene upon the abovementioned treatments. Methods: We cultured MCF-7 cancer cells in complete cell culture media and subsequently subjected them to increasing concentrations (0 - 200 μg/mL) of the extract. The cytotoxic activity of the extract was investigated using an MTT assay. The quantitative analysis of ODC1 gene expression was performed using real-time PCR. Results: The cell viability was significantly decreased in concentration- and time-dependent manners. The mRNA expression of the ODC1 gene declined gradually with the increasing concentrations of extracts. Conclusions: Our findings indicated that R. khorasanicum extract could potentially influence ODC1 gene expression in breast cancer cells and exert inhibitory effects on cancer cell proliferation.

Regulation of Interleukin-36γ/IL-36R Signaling Axis by PIN1 in Epithelial Cell Transformation and Breast Tumorigenesis.

Simple SummaryMembers of the interleukin (IL)-1 cytokine family exhibit dual functions in the regulation of inflammation and cancer. Recent studies have shown the critical role of IL-36γ, the newly identified IL-1 family member, in the regulation of cellular processes implicated in the progression of cancer. Therefore, the underlying mechanism of IL-36γ in tumor development is of considerable interest. Here, we identified the pivotal role of IL-36γ in the proliferation of breast cancer cells. Consistently, IL-36γ was found to promote epithelial cell transformation via the activation of c-Fos, c-Jun, and AP-1 transcription factors, followed by the IL36R-mediated MEK/ERK and JNK/c-Jun cascades. Furthermore, our findings demonstrate the critical role of PIN1 in the regulation of IL-36γ-induced mammary gland tumorigenesis. Given the increasing recognition of the relationship between IL-1 cytokines, inflammation, and cancer, the significance of distinct members of the IL-1 cytokine family in the etiology of cancer has been widely researched. In the present study, we investigated the underlying mechanism of the IL-36γ/IL-36R axis during breast cancer progression, which has not yet been elucidated. Initially, we determined the effects of IL-36γ on the proliferation and epithelial cell transformation of JB6 Cl41 mouse epidermal and MCF7 human breast cancer cells using BrdU incorporation and anchorage-independent growth assays. We found that treatment with IL-36γ increased the proliferation and colony formation of JB6 Cl41 and MCF7 cells. Analysis of the mechanism underlying the neoplastic cell transformation revealed that IL-36γ induced IL-36R-mediated phosphorylation of MEK1/2, ERK1/2, JNK1/2, and c-Jun, resulting in increased c-Fos, c-Jun, and AP-1 activities in JB6 Cl41 and MCF7 cells. Furthermore, the IL-36γ-induced tumorigenic capacity of MCF7 cells was considerably enhanced by PIN1, following MEK/ERK and JNK/c-Jun signaling. Interestingly, blocking PIN1 activity using juglone suppressed the IL-36γ-induced increase in the anchorage-independent growth of 4T1 metastatic mouse breast cancer cells. Finally, in a syngeneic mouse model, IL-36γ-induced tumor growth in the breast mammary gland was significantly inhibited following PIN1 knockout.

Anticancer activity of micropropagated Hedychium coronarium rhizome essential oil

Cancer is a life threatening disease than any other diseases which is leading to death throughout the world. The natural products should be explored as anticancer agents which are not expensive, easily available and most beneficial to humans. Today the current research is being done on secondary metabolites and bioactive compounds present in the medicinal plants alongwith their therapeutic properties. Zingiberaceae family from centuries is used as spices and bears vast pharmacological activities including Hedychium coronarium. Also another most important characteristic of this family is the aromatic essential oil present in its leaves and rhizomes. In the present study, Hedychium coronarium rhizome essential oils were treated against human breast cancer cell line or MCF7 and human cervical cancer cell line or HeLa by MTT assay. For validation of the cytotoxic activity, MCF7 and HeLa cell were used against various concentrations of aromatic rhizome essential oil respectively. This study revealed that bioactive compound present in rhizome oil was most significantly active when tested against MCF7 and HeLa cell line.

Curcumin Induces MCF-7 Cells Pyroptosis via Autophagy/CTSB/NLRP3/ Caspase-1/GSDMD Signaling Pathway in Vitro and Vivo

Background: Curcumin, as a lipid-lowering drug, has been reported to be effective in the treatment of breast cancer. However, the underlying molecular mechanisms have not been completely investigated. Methods: MTT assay was used to determine the effect of curcumin on survival rate of MCF-7 cells. The effects of curcumin on tumor growth were observed in animal models of breast cancer. The positive reactions of Caspase-1, IL-1β and IL-18 were detected by immunohistochemistry. LC3, p62, CTSB, ASC, Pro-Caspase-1, GSDMD, NLRP3, Caspase-1, GSDMD-N, IL-1β and IL-18 were determined by Western blot in vitro and vivo. ELISA determined the release of extracellular IL-1β and IL-18. LDH release was measured. The expression level of CTSB in cytoplasm were determined by immunofluorescence assay. Cell proliferation, cell migration and tube formation assays were used to determine the abilities of cells. In this study, NLRP3 inflammasome inhibitor MCC950, cathepsin B inhibitor CA-074 ME and autophagy inhibitor 3-MA were used to act on cells to investigate the role of NLRP3 inflammasome, cathepsin B and autophagy in curcumin-induced pyro ptosis of MCF-7 breast cancer cells. Results: In mouse model of breast cancer, we observed that curcumin treatment significantly induced cell autophagy and pyro ptosis. In human breast cancer MCF-7 cells, we found that curcumin induced pyrophoric cell death was dependent on the activation of NLRP3/Caspase-1/GSDMD signaling pathway, which was CTSB-dependent. In addition, curcumin-induced cell autophagy caused lysosomal rupture and CTSB release. Furthermore, NLRP3 inhibitor (MCC950) significantly suppressed curcumin-induced pyro ptosis, as well as CTSB inhibitor (CA074 Me) and autophagy inhibitor (3-MA). Besides, we also found that curcumin suppressed cell proliferation, cell migration and tube formation, which could be reversed by inhibitors. Conclusions: In summary, our results demonstrated that curcumin induced MCF-7 cell pyro ptosis by the activation of autophagy/CTSB/NLRP3/Caspase-1/GSDMD signaling pathway. These findings offer novel insights into the potential molecular mechanisms of curcumin in treatment of breast cancer

Thermosensitive Hydrogels Loaded with Resveratrol Nanoemulsion: Formulation Optimization by Central Composite Design and Evaluation in MCF-7 Human Breast Cancer Cell Lines.

The second most common cause of mortality among women is breast cancer. A variety of natural compounds have been demonstrated to be beneficial in the management of various malignancies. Resveratrol is a promising anticancer polyphenolic compound found in grapes, berries, etc. Nevertheless, its low solubility, and hence its low bioavailability, restrict its therapeutic potential. Therefore, in our study, we developed a thermosensitive hydrogel formulation loaded with resveratrol nanoemulsion to enhance its bioavailability. Initially, resveratrol nanoemulsions were formulated and optimized utilizing a central composite-face-centered design. The independent variables for optimization were surfactant level, homogenization speed, and time, while the size and zeta potential were the dependent variables. The optimized nanoemulsion formulation was converted into a sensitive hydrogel using poloxamer 407. Rheological studies proved the formation of gel consistency at physiological temperature. Drug loading efficiency and in vitro drug release from gels were also analyzed. The drug release mechanisms from the gels were assessed using various mathematical models. The effect of the optimized thermosensitive resveratrol nanoemulsion hydrogel on the viability of human breast cancer cells was tested using MCF-7 cancer cell lines. The globule size of the selected formulation was 111.54 ± 4.16 nm, with a zeta potential of 40.96 ± 3.1 mV. Within 6 h, the in vitro release profile demonstrated a release rate of 80%. According to cell line studies, the produced hydrogel of resveratrol nanoemulsion was cytotoxic to breast cancer cells. Overall, the results proved the developed nanoemulsion-loaded thermosensitive hydrogel is a promising platform for the effective delivery of resveratrol for the management of breast cancer.

Synthesis and Biological Evaluation of Arylamide Sulphonate Derivatives as Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 and -3 Inhibitors.

Aberrant level of ectonucleotide pyrophosphatase/phosphodiesterase-1 and -3 is linked with numerous disorders, for instance, diabetes, cancer, osteoarthritis, chondrocalcinosis, and allergic reactions. These disorders may be cured or minimized by blocking the activity of ENPP1 and ENPP3 isozymes. In this study, arylamide sulphonates were synthesized, characterized, and evaluated for their capability to affect the activity of isozymes ENPP1 and ENPP3. Among the selective inhibitors of ENPP1, compounds 4f and 4q exhibited sub-micromolar IC50 values of 0.28 ± 0.08 and 0.37 ± 0.03 μM, respectively, followed by 7a, with IC50 equal to 0.81 ± 0.05 μM, whereas out of the selective inhibitors of isozyme ENPP3, 4t and 7d preferably lessened the activity to half of the maximal inhibitory concentration of 0.15 ± 0.04 and 0.16 ± 0.01 μM alternatively. In addition, many structures including 4c, 4g, 4k, 4l, 4n, 4o, 4r, 4s, 7b, 7c, and 7e inhibited the activity of both isozymes to a significant level. Enzyme kinetic study of compound 4j revealed an uncompetitive mode of inhibition of ENPP1 isozyme, while 7e competitively blocked the activity of ENPP3. Cell viability analysis revealed the compound 4o as a cytotoxic agent against MCF7 (human breast cancer cell line) with a percentage inhibition of 63.2 ± 2.51%, whereas compounds 4c, 4d, 4n, and 7d decreased the HeLa cell viability (human cervical cancer cell line) to more than 50%. The tested compounds were non-cytotoxic against HEK293 (a human embryonic kidney cell line). Molecular docking analysis of selected inhibitors of both isozymes produced optimistic interactions with the influential amino acids, such as Leu290, Lys295, Tyr340, Asp376, His380, and Pro323 of ENPP1, whereas residues Asn226, His329, Leu239, Tyr289, Pro272, Tyr320, and Ala205 of ENPP3 crystallographic structure formed interactions with the potent inhibitors.

Combination of Goniothalamin and Sol-Gel-Derived Bioactive Glass 45S5 Enhances Growth Inhibitory Activity via Apoptosis Induction and Cell Cycle Arrest in Breast Cancer Cells MCF-7.

Background Combination of natural products with chemically synthesised biomaterials as cancer therapy has attracted great interest lately. Hence, this study is aimed at investigating the combined effects of goniothalamin and bioactive glass 45S5 (GTN-BG) and evaluating their anticancer properties on human breast cancer cells MCF-7. Methods The BG 45S5 was prepared using the sol-gel process followed by characterisation using PSA, BET, SEM/EDS, XRD, and FTIR. The effects of GTN-BG on the proliferation of MCF-7 were assessed by MTT, PrestoBlue, and scratch wound assays. The cell cycle analysis, Annexin-FITC assay, and activation of caspase-3/7, caspase-8, and caspase-9 assays were determined to further explore its mechanism of action. Results The synthesised BG 45S5 was classified as a fine powder, having a rough surface, and contains mesopores of 12.6 nm. EDS analysis revealed that silica and calcium elements are the primary components of BG powders. Both crystalline and amorphous structures were detected with 73% and 27% similarity to Na2Ca2(Si2O7) and hydroxyapatite, respectively. The combination of GTN-BG was more potent than GTN in inhibiting the proliferation of MCF-7 cells. G0/G1 and G2/M phases of the cell cycle were arrested by GTN and GTN-BG. The percentage of viable cells in GTN-BG treatment was significantly lower than that in GTN. In terms of activation of initiator caspases for both extrinsic and intrinsic apoptosis pathways, caspase-8 and caspase-9 were found more effective in response to GTN-BG than GTN. Conclusion The anticancer effect of GTN in MCF-7 cells was improved when combined with BG. The findings provide significant insight into the mechanism of GTN-BG against MCF-7 cells, which can potentially be used as a novel anticancer therapeutic approach.

Glutathione-depleted and cancer-targeted nanocapsules encapsulating bimetallic oxide nanoparticles for enhanced chemo-sonodynamic therapy

Sonodynamic therapy (SDT) has emerged as a promising noninvasive therapeutic modality due to its deep tissue penetration depth. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanocapsules encapsulating oxygen-deficient MnWOx nanoparticles (NPs) and doxorubicin (DOX) were fabricated for chemo-sonodynamic combination therapy against cancer. To achieve cancer-targeted chemo-SDT, PLGA was conjugated to a cancer-targeting biotin through poly(ethylene glycol) (PEG). Biotin-PEG-PLGA (BP-PLGA) nanocapsules encapsulating DOX and hydrophobic MnWOx NPs (BP-PLGA-DOX@MnWOx) exhibited high physiological stability and pH-responsive drug release. The oxygen-deficient MnWOx NPs enabled US-triggered generation of singlet oxygen and hydroxyl radicals owing to their oxygen-deficient structures that prevent electron–hole recombination. Glutathione (GSH) depletion by MnWOx-loaded PLGA nanocapsules was observed in MCF-7 human breast cancer cells, which leads to augmented intracellular ROS levels and sonodynamic effects. Notably, BP-PLGA-DOX@MnWOx greatly improved cellular uptake by breast cancer cells, resulting in efficient intracellular delivery of DOX and MnWOx NPs. As a result, BP-PLGA-DOX@MnWOx exhibited efficient and cancer-targeted cytotoxicity in MCF-7 cells upon US irradiation. This study demonstrates that BP-PLGA-DOX@MnWOx nanocapsules are promising cancer-targeting nanosonosensitizers for efficient chemo-sonodynamic cancer therapy.

Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells.

Polyamine levels decrease with menopause; however, little is known about the mechanisms regulated by menopause. In this study, we found that among the genes involved in the polyamine pathway, polyamine oxidase (PAOX) mRNA levels were the most significantly reduced by treatment with 17β-estradiol in estrogen receptor (ESR)-positive MCF-7 breast cancer cells. Treatment with 17β-estradiol also reduced the PAOX protein levels. Treatment with selective ESR antagonists and knockdown of ESR members revealed that estrogen receptor 2 (ESR2; also known as ERβ) was responsible for the repression of PAOX by 17β-estradiol. A luciferase reporter assay showed that 17β-estradiol downregulates PAOX promoter activity and that 17β-estradiol-dependent PAOX repression disappeared after deletions (−3126/−2730 and −1271/−1099 regions) or mutations of activator protein 1 (AP-1) binding sites in the PAOX promoter. Chromatin immunoprecipitation analysis showed that ESR2 interacts with AP-1 bound to each of the two AP-1 binding sites. These results demonstrate that 17β-estradiol represses PAOX transcription by the interaction of ESR2 with AP-1 bound to the PAOX promoter. This suggests that estrogen deficiency may upregulate PAOX expression and decrease polyamine levels.

Static or 50 Hz magnetic fields at 100 µT do not modify the clonogenic survival of doxorubicin-treated MCF-7 cancer cells

The objective of this study was to evaluate whether static or 50 Hz magnetic fields (MFs) modify responses to the chemotherapeutic agent doxorubicin in human MCF-7 breast cancer cells. To this end, cells were exposed to static or 50 Hz MFs at 100 µT with or without doxorubicin for 3 h. Following the exposures, cytosolic and mitochondrial superoxide levels, DNA damage levels, and the clonogenic survival of the cells were evaluated. It was found that static MFs decreased the DNA damage level induced by doxorubicin treatment (p = 0.023), but no effects were observed for either cytosolic and mitochondrial superoxide levels or the clonogenic survival of the cells. On the other hand, 50 Hz MF increased doxorubicin-induced cytosolic superoxide levels (p = 0.016), while the mitochondrial superoxide level, DNA damage level, and clonogenic survival were unaffected. In conclusion, we found that static and 50 Hz MFs may modify responses to doxorubicin treatment, but the subsequent survival of the doxorubicin-treated cancer cells was unaffected by both types of MFs. Therefore, the present results suggest that static or 50 Hz MFs for 3 h do not modify the efficacy of doxorubicin in MCF-7 cancer cells.

Machine learning-based screening of MCF-7 human breast cancer cells and molecular docking analysis of essential oils from Ocimum basilicum against breast cancer

A machine learning algorithm-based model is a powerful tool for discovering candidate compounds on the breast cancer cell line MCF-7. Using the Lazy Predict Python package, the “Random Forest” algorithm indicates that the highest accuracy is 83.57% in discovering potential compounds. Essential oils from the leaves and stems of Ocimum basilicum, as identified by GC−MS analysis, are selected as a test dataset. Among them, eight essential oils, including alpha-pinene, trans-beta-ocimene, estragole, alpha-cubebene, gamma-muurolene, delta-cadinol, gamma-cadinene, and beta-ocimene potentially exhibit activity against MCF-7. The anticancer mechanisms of these essential oils are analyzed using molecular docking simulation based on the structure-activity relationship between these candidates and the two protein targets, BRCA1 and BRCA2. This study shows that our model can potentially screen bioactive compounds targeting breast cancer cell line MCF-7 and offer the basis for further research into substances derived from Ocimum basilicum that can potentially be utilized as a novel treatment for breast cancer.

Cytotoxic and Antibacterial Properties of Resveratrol Oligomers from the Stem Bark of Dryobalanops rappa

Background: Dryobalanops rappa is a plant species belonging to the family of Dipterocarpaceae. Nevertheless, the active compounds present in D. rappa have never been investigated. Objective: The aim of this research is to isolate and characterize compounds from Dryobalanops rappa and to study its bioactivity against human MCF-7 breast cancer and A549 lung cancer cell lines and several bacterial strains. Methods: The isolation step was carried out using a combination of chromatographic techniques. The structure of the isolated compounds was elucidated mainly using NMR spectroscopy. The cytotoxic activity of isolated compounds was determined with MTT assay, and the antimicrobial was screened using a modified resazurin microtiter-plate assay. Results: Isolation and purification of methanolic extract of D. rappa stem bark yielded 14 known oligomeric resveratrol types of compounds (1-14). Results showed that isolated ampelopsin E (5) and vaticanol C (14) displayed moderate activity against human MCF-7 breast cancer and A549 lung cancer cell lines with IC50 values 14.3 and 10.7 μg/mL, respectively. Interestingly, acetate derivative of isolated laevifonol (2) and ampelopsin F (3) was found to possess potent activities towards MCF-7 cancer cell line with IC50 values 2.8 and 3.3 μg/mL, respectively, in comparison to the parental compounds that demonstrated weak activities (IC50 > 50 μg/mL). For the antibacterial assay, compounds 10 and 12 showed moderate activities towards Gram-positive bacterial strains (MIC ≤ 50 μM). Conclusion: 14 known oligomeric resveratrol types of compounds have been isolated. The activity of 14 against A549 cell line, 5 against MCF-7 cell line, and 10 and 12 against Gram-positive bacterial strains were the most promising results of this study. While the strong cytotoxicity of acetate derivative (2 and 3) against MCF-7 cell line has revealed the potential of resveratrol oligomers to be used as a template for designing new anticancer drugs.