Breast Adenocarcinoma MCF-7 Cells Research Articles

Unveiling the therapeutic potential of anthocyanin/cisplatin-loaded chitosan nanoparticles against breast and liver cancers

Abstract Background Liver and breast cancers are among the leading causes of cancer-related deaths worldwide, prompting researchers to seek natural anticancer agents and reduce chemotherapy side effects. Red beetroot (Beta vulgaris Linnaeus), rich in polyphenols and powerful antioxidants, has shown potential in cancer prevention. This study aimed to evaluate the impact of red beetroot-derived anthocyanin (Ant), Ant-loaded chitosan nanoparticles (Ant NPs), cisplatin (Cis), Cis-loaded chitosan (Cis NPs), and Cis + Ant-loaded chitosan NPs on human hepatoma HepG2 and breast adenocarcinoma MCF7 cell lines. Methods NPs preparation was evaluated by zeta potential, FTIR, and SEM. The cytotoxic, apoptotic, antioxidant, anti-inflammatory, anti-metastatic, and anti-angiogenic effects were assessed by MTT assay, qPCR, AO/EB staining, and flow cytometry. Results Treatment with Ant, Ant NPs, Cis, Cis NPs, and Cis + Ant NPs caused cytotoxicity in HepG2 and MCF7 with best effect in Cis-treated cells. The anticancer effects were attributed to mitochondrial-dependent apoptosis (with high Bax and low Bcl2 expression), chromatin disintegration, and cell cycle arrest in G2/M and S phases. All treatments inhibited migration by downregulating the migration-related gene MMP9 and upregulating the anti-migratory gene TIMP1 and decreased the angiogenesis-related gene VEGF and the inflammatory gene TNFα with best results in Cis NPs-treated cells. Interestingly, Ant, Ant NPs, and Cis + Ant NPs increased the antioxidant status (high GSH and upregulated expression of Nrf2 and OH-1) and decreased drug resistance-related MAPK1 and MDR1 genes compared to Cis and Cis NPs-treated cells. Conclusions Anthocyanin and cisplatin-loaded chitosan nanoparticles effectively combat breast and liver cancers by inducing cancer cell apoptosis, enhancing antioxidant defenses, and reducing inflammation. They also inhibit tumor spread and blood vessel formation through downregulation of MMP9 and VEGF, highlighting their therapeutic potential.

B-351 Genotoxic Producing Escherichia coli Protects and Promotes Breast Adenocarcinoma

Abstract Background Recent studies have linked certain colibactin producing subphylas of E. coli to colorectal cancer. The bacterium synthesizes colibactin via the pks genomic island containing a series of clbA to clbS genes. The genotoxin causes inter-strand DNA cross-links, which lead to double strand breaks and promotion of colorectal adenocarcinoma. The published studies have prioritized the colorectal regions of the body where E. coli is commonly found, but none have identified the same genotoxic relationship with other types of adenocarcinoma. In this study, we evaluate DNA damage and cellular changes of mammary breast tissue based on high and low levels of colibactin producing E. coli exposure. The goal is to evaluate if colibactin can affect cells in the mammary breast tissue promoting breast adenocarcinoma growth. Methods Two cell lines were acquired from ATCC: primary mammary epithelial cells (PCS-600-010) and MCF-7 breast adenocarcinoma cells (HTB-22). Both cell lines were split into six culture flasks and maintained until ∼80% confluence was reached using the ATCC cell culture protocols. Once all the flasks had reached the target confluence, they were divided into exposure groups of high and low concentrations of colibactin producing E. coli, a group of non-colibactin producing E. coli, a group exposed only to phosphate buffered saline, and a control group with no exposure. Cellular morphology was observed using light microscopy before, after exposure, and every 5 minutes up to 15 minutes. E. coli and colibactin DNA concentrations were quantified using quantitative polymerase chain reaction. Genomic DNA was extracted from each group of cells. The DNA from each group was whole genome sequenced and analyzed for genomic variation. Results The normal cells exposed to E. coli showed immediate lysing and continued to lyse after a 5 minute incubation; however, the adenocarcinoma positive cells showed no lysing up to 30 minutes incubation. Sequencing results show genomic variation between the groups and specific break points associated with the E. coli exposed groups. Conclusions Our results show that the presence of E. coli with mammary breast tissue can destroy normal tissue, promote lysis resistance, and allow adenocarcinoma cells to continue to grow. The colibactin producing E. coli does cause double stranded breaks and can lead to cell death. This new information points out a critical need to monitor the microbiome and infection levels of people at risk or in early stages of cancer to prevent adenocarcinoma growth and destruction of normal tissue. This study indicates that colibactin producing E. coli may play a larger role in tissue damage and promotion of other types of cancer. More research is needed to elucidate the molecular pathway and mechanisms of colibactin, which will lead to new diagnostics or therapeutics that monitor E. coli levels or inhibit colibactin’s toxic effects.

Antiproliferative potential of Plinia edulis leaves

Plinia edulis, popularly known as ‘cambucá’, is used in Brazilian folk medicine to treat several conditions. The aim of this study was to evaluate the mutagenicity and cytotoxicity of cambucá leaf extract, as well as its antioxidant activity. The ‘Ames’ test and Orac assay were used to evaluate the mutagenicity and antioxidant activity, respectively, and the phytochemical analysis of the ethanol leaf extract (LE) was performed by chromatographic and spectrometric methods. The in vitro cytotoxicity was tested on CHO (Chinese Hamster Ovary) cells and on nine human tumor cell lines. Phytochemical analysis of LE has revealed the presence of triterpenes and flavonoids. The LE did not show mutagenicity at the concentration of 20 mg plate-1 and exhibited high antioxidant activity, with Orac value of 3948 µmol TE g-1. The LE and its fractions (ethyl acetate; methanol) showed antiproliferative activity against cancer cell lines and proliferative activity in normal cells. The ethyl acetate fraction was the most active extract, presenting antiproliferative activity against strains of breast cancer, prostate cancer, colon cancer, lung cancer, melanoma and leukemia (GI50 0.01-8.57 µg mL-1), being more effective than the reference drug (doxorubicin) against human breast adenocarcinoma MCF-7 cell line. These results suggest P. edulis as a potential adjuvant in cancer therapy and chemoprevention.

Novel Thiazole-Hydrazide Derivatives and Their Anticancer Properties

Objective: Cancer is described as uncontrolled cell division, and it is a major problem in Türkiye, as well as around the world. Current treatment options are insufficient in some cases, particularly the treatment rate for lung cancer cases, which is very low. Meanwhile, current pharmaceuticals have several side effects, such as drug-drug interactions, and cognitive disorders. Additionally, developing drug resistance is a major problem for current and future management of the disease. Accordingly, the search for new molecules or alternative treatment options is actively achieved. Methods: In this study, eight novel thiazole-hydrazide analogs were designed and synthesized, and their structural elucidation was performed via HRMS, 1H-NMR, and 13C-NMR. Their biological activity profile was investigated on A549 lung carcinoma and MCF7 breast adenocarcinoma cells. To determine the selective cytotoxicity on cancer cells, they were also tested against NIH/3T3 healthy cell line. Besides that, an in silico study was performed to understand the binding modes of the compounds. Results: The results showed that in the serial 4f and 4g, the most bulky analogues, showed no inhibition against any cell type, even at the highest concentration tested. On the other hand, 4a, 4b, 4d, 4e, and 4h showed less cytotoxicity on healthy cells than A549 cells, so they exhibited significant cytotoxicity and a selective profile against A549 cancer cells. While they also inhibited MCF7 cells. The major point is that para-chlorophenyl analogs at the fourth position on thiazole (4a and 4d) displayed a better anticancer profile than ortho-chlorophenyl analogs. These two compounds were also investigated for their apoptotic effects using in silico studies. Both experimental and in silicon studies revealed that the combination of thiazole and hydrazinoacetyl has a significant impact against cancer cells, and in silico study also suggested that tri-substitute thiazole ring has anticancer potential that induced cancer cell death via apoptosis. Conclusion: Results of this study was presented that compound 4a was the most potent compound against lung cancer cells (A549) and 4d was the most potent compound against breast cancer cells (MCF-7). Furthermore, analyzing the molecular docking study for promising compounds (4a and 4d) suggested that interactions with the loop region residues have a pivotal role in inducing caspase-3 enzyme activity. It was concluded that hybridization of thiazole and hydrazinoacetyl moieties is responsible for the anticancer activity.

Affinity for Estrogen Receptor α (ERα) in a <i>trans</i>-Stilbene Derivative Containing a Pyridoxine Fragment

Molecular targets for a promising antitumor agent based on trans-stilbene containing a pyridoxine fragment were identified. The lead compound, (E)-6-(3,4-dimethoxystyryl)-2,2,5,8-tetramethyl-4H-[1,3] dioxino[4,5-c]pyridine, was found to selectively induce apoptosis in MCF-7 breast adenocarcinoma cells overexpressing estrogen receptor, but not in MDA-MB-231 cells negative for estrogen receptor. The mechanism by which the novel trans-stilbene derivative acts as a selective estrogen receptor modulator was analyzed, and the affinity for human estrogen receptor α (ERα) was assessed by fluorescence polarization. Unlike its structural analogs—tamoxifen and raloxifene, the lead compound showed no affinity for ERα and did not form complexes with it. Therefore, it was concluded that the selective action of the pyridoxine-containing derivative of trans-stilbene on estrogen-positive breast cancer cells occurs through an alternative mechanism. The EC 50 values for the displacement of the fluorescent ligand from the ERα active site were 22, 120, and 595 nM for estradiol, raloxifene, and tamoxifen, respectively.

Synthesis, Anticancer Activity, and Docking Studies of Novel Hydroquinone-Chalcone-Pyrazoline Hybrid Derivatives.

A novel series of antitumor hybrids was synthesized using 1,4-benzohydroquinone and chalcone, furane, or pyrazoline scaffolds. This were achieved through isosteric substitution of the aryl group of the chalcone β-carbon with the furanyl moiety and structural modification of the α,β-unsaturated carbonyl system. The potential antitumor activity of these hybrids was evaluated in vivo on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, demonstrating cytotoxic activity with IC50 values ranging from 28.8 to 124.6 µM. The incorporation of furan and pyrazoline groups significantly enhanced antiproliferative properties compared to their analogues and precursors (VII-X), which were inactive against both neoplastic cell lines. Compounds 4, 5, and 6 exhibited enhanced cytotoxicity against both cell lines, whereas compound 8 showed higher cytotoxic activity against HT-29 cells. Molecular docking studies revealed superior free-energy values (ΔGbin) for carcinogenic pathway-involved kinase proteins, with our in silico data suggesting that these derivatives could be promising chemotherapeutic agents targeting kinase pathways. Among all the synthesized PIBHQ compounds, derivatives 7 and 8 exhibited the best drug-likeness properties, with values of 0.53 and 0.83, respectively. ADME results collectively suggest that most of these compounds hold promise as potential candidates for preclinical assays.

Matrix Metallopeptidase 3 Coding SNPS Suppress Cell Invasion in MCF7 Breast Cancer Cells

Matrix metallopeptidase 3 (MMP3) is among the key players in breast cancer metastasis that contributes to the highest cancer-related deaths in females globally. Previously, in silico analyses had shown that several coding single nucleotide polymorphisms (SNPs) of MMP3 were predicted to alter the secondary structures of MMP3 and subsequently reduce its mRNA stability. To validate the mentioned hypotheses, this study aimed to determine the effects of six coding SNPs of MMP3 on its mRNA stability, protein expression level as well as cell invasiveness in vitro. In this study, breast adenocarcinoma MCF7 cells were transfected with MMP3 wild type (MMP3-WT) and a variant containing SNPs (MMP3-Var). Following transfection, protein expression level, mRNA stability and enzyme activity of MMP3-WT and MMP3-Var were evaluated. Finally, the effect of MMP3 coding SNPs on cell invasiveness in breast cancer was determined. In this study, the mRNA stability, protein expression level and enzymatic activity of MMP3-Var were significantly reduced. Moreover, the presence of MMP3 coding SNPs led to attenuated invasiveness of transfected MCF7 cells. In conclusion, these findings may contribute to the current understanding of these coding SNPs with metastasis in breast cancer.

Synthesis, cytotoxicity and antioxidant activity of new conjugates of N-acetyl-d-glucosamine with α-aminophosphonates

A series of the first conjugates of N-acetyl-d-glucosamine with α-aminophosphonates was synthesized using the Kabachnik-Fields reaction, the Pudovik reaction, a copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) and evaluated for the in vitro cytotoxicity against human cancer cell lines M − HeLa, HuTu-80, A549, PANC-1, MCF-7, T98G and normal lung fibroblast cells WI-38. The tested conjugates, with exception of compound 21b, considered as a lead compound, were either inactive against the used cancer cells or showed moderate cytotoxicity in the range of IC50 values 33−80 μM. The lead compound 21b, being non cytotoxic against normal human cells WI-38 (IC50 = 90 μM), demonstrated good activity (IC50 = 17 μM) against breast adenocarcinoma cells (MCF-7) which to be 1.5 times higher than the activity of the used reference anticancer drug tamoxifen (IC50 = 25.0 μM). A flexible receptor molecular docking simulation showed that the cytotoxicity of the synthesized conjugates of N-acetyl-d-glucosamine with α-aminophosphonates against breast adenocarcinoma MCF-7 cell line is due to their ability to inhibit EGFR kinase domain. In addition, it was found that conjugates 22a and 22b demonstrated antioxidant activity that was not typical for α-aminophosphonates.

Phyto-synthesized silver nanoparticles from Sargassum subrepandum: anticancer, antimicrobial, and molluscicidal activities.

In the realm of nanotechnology, the use of algae to produce nanoparticles is an environmentally friendly, sustainable, and economically viable strategy. In the present study, the brown macroalgae Sargassum subrepandum was utilized to effectively produce silver nanoparticles (AgNPs). Through various characterization techniques, the AgNPs' structural integrity was confirmed. AgNPs exhibited significant antimicrobial activity against Pseudomonas aeruginosa and Fusarium equiseti. AgNPs showed cytotoxic effects on the MCF-7 breast adenocarcinoma cell line with an IC50 of 12.5 µg/ml. Treatment with AgNPs resulted in a marked reduction in cell viability, alongside evident apoptotic and necrotic morphological changes in the cancer cells. Through molecular docking studies, a deeper understanding of the interaction between AgNPs and crucial proteins related to cancer has been achieved, AgNPs showed a promising molluscicidal action on Biomphalaria alexandrina snails, a Schistosoma mansoni intermediate host. The half-lethal dose (LC50) of AgNPs was determined to be 0.84 mg/L. The potential consequences of its administration include potential disruptions to the glycolysis profile, as well as potential impacts on the steroidal hormone's estrogen and testosterone and certain kidney function tests. This study highlights the diverse uses of algae-synthesized AgNPs, ranging from healthcare to environmental management, demonstrating their importance in advancing nano-biotechnological solutions.

Phytochemical profiling, cytotoxic, anti-migration, and anti-angiogenic potential of phenolic-rich fraction from Peganum harmala: in vitro and in ovo studies.

Peganum harmala has been extensively employed in Algerian traditional medicine practices. This study aimed to explore the impact of n-butanol (n-BuOH) extract sourced from Peganum harmala seeds on cell proliferation, cell migration, and angiogenesis inhibition. Cytotoxic potential of n-BuOH extract was evaluated using MTT (3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyltetrazolium bromide) assay against human breast adenocarcinoma MCF-7 cells, cell migration was determined using scratch assay, and anti-angiogenic effect was evaluated through macroscopic and histological examinations conducted on chick embryo chorioallantoic membrane. Additionally, this research estimated the phytochemical profile of n-BuOH extract. Fifteen phenolic compounds were identified using Ultra-performance liquid chromatography UPLC-ESI-MS-MS analysis. In addition, the n-BuOH extract of P. harmala exhibited potent antioxidant and free radical scavenging properties. The n-BuOH extract showed potent cytotoxicity against MCF-7 cell with an IC50 value of 8.68 ± 1.58 μg/mL. Furthermore, n-BuOH extract significantly reduced migration. A strong anti-angiogenic activity was observed in the groups treated with n-BuOH extract in comparison to the negative control. Histological analysis confirmed the anti-angiogenic effect of the n-BuOH extract. This activity is probably a result of the synergistic effects produced by different polyphenolic classes.

Fabrication and characterization of a new eco-friendly sulfonamide-chitosan derivative with enhanced antimicrobial and selective cytotoxicity properties

Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance. The results of scanning electron microscopy, thermal gravimetric analysis, and X-ray diffraction indicated that the morphology changed to a porous nature, the thermal stability decreased, and the crystallinity increased in the DMS-CH derivative compared to chitosan, respectively. The degree of substitution was calculated from the elemental analysis data and was found to be moderate (42%). The modified chitosan exhibited enhanced antimicrobial properties at low concentrations, with a minimum inhibitory concentration (MIC) of 50 µg/mL observed for B. subtilis and P. aeruginosa, and a value of 25 µg/mL for S. aureus, E. coli, and C. albicans. In the case of native chitosan, the MIC values doubled or more, with 50 µg/mL recorded for E. coli and C. albicans and 100 μg/mL recorded for B. subtilis, S. aureus, and P. aeruginosa. Furthermore, toxicological examinations conducted on MCF-7 (breast adenocarcinoma) cell lines demonstrated that DMS-CH exhibited greater toxicity (IC50 = 225.47 μg/mL) than pure CH, while still maintaining significant safety limits against normal lung fibroblasts (WI-38). Collectively, these results suggest the potential use of the newly modified chitosan in biomedical applications.

Cytotoxic and apoptotic effects of Ferula gummosa Boiss: extract on human breast adenocarcinoma cell line.

Ferula gummosa Boiss. is a well-known and valuable medicinal plant in Iran. Research has shown that this plant has several pharmacological properties, including anti-bacterial, anti-cancer and etc. In the present study, we investigated the cytotoxic properties of F. gummosa Boiss. extract in MCF-7 breast adenocarcinoma cells. The cytotoxicity and pro-apoptotic properties of the extract were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test and propidium iodide (PI) stained cells, respectively. Apoptosis and necrosis were evaluated by annexin V-PI staining. The levels of reactive oxygen species (ROS),malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) was determined to evaluate oxidative stress. The cell migration and the gene expression were assessed by scratch assay and quantitative real-time polymerase chain reaction (q-RT-PCR), respectively. The extract of F. gummosa decreased the viability and cell cycle progression of MCF-7 cells by inducing apoptosis and necrosis, increasing ROS and MDA levels, and decreasing GSH levels and SOD activity. It also lowered the cells' migration capability by enhancing p53 mRNA levels and reducing MMP-9 mRNA expression. F. gummosa exhibited pro-apoptotic, anti-proliferative, and anti-metastatic effects on MCF-7 cells. It is therefore recommended that detailed future research be done on different parts of the plant or its secondary metabolites to find anti-cancer lead compounds.

Sequential assembly of DNA nanoparticles inside cells enables lysosome interference and cell behavior regulation

The artificial manipulation of exogenous molecules in living cells is a promising means to regulate cellular behaviors. However, the spatiotemporal control of self-assembly within the complex intracellular environment remains grand challenge. Herein, we report a controlled sequential assembly of DNA nanoparticles in living cells, responding to acidic environment in lysosome, which enables lysosome interference and subsequently regulates a series of cellular behaviors. Two types of ultra-long DNA chains (DNA-chain-1 and 2) synthesized via rolling circle amplification were compressed by magnesium ion to two DNA nanoparticles (DNP-1 and 2), respectively. In the acidic environment of lysosomes, both DNP-1 and DNP-2 dissociated to DNA chains, and the DNA chains were subsequently assembled through base-pairing to form a hydrogel. This sequential assembly process consumed hydrogen ions within the lysosome, decreased lysosomal acidity, and thus altered the hydrolase activity and lysosomal membrane permeability. The interference of sequential assembly on lysosomes promoted cell movement in human breast adenocarcinoma MCF-7 cells, with 81.19% and 36.24% enhancement in cell migration and invasion capacity, respectively; the level of cellular autophagy was increased by 170.00%. Our study provides a new strategy for the sequential assembly of exogenous DNA materials in living cells.

Cytotoxicity of bismuth(III) dithiocarbamate derivatives by promoting a mitochondrial-dependent apoptotic pathway and suppressing MCF-7 breast adenocarcinoma cell invasion.

We previously reported that the bismuth(III) dithiocarbamate derivative, bismuth diethyldithiocarbamate (1) exhibited greater cytotoxicity while inducing apoptosis via the intrinsic pathway in MCF-7 cells. We further evaluated the other bismuth(III) dithiocarbamate derivatives, Bi[S2CNR]3, with R = (CH2CH2OH)(iPr), (CH2)4, and (CH2CH2OH)(CH3), denoted as 2, 3, and 4, respectively, in the same MCF-7 cell line. 2-4 were found to exhibit IC50 values of 10.33 ± 0.06µM, 1.07 ± 0.01µM and 25.37 ± 0.12µM, respectively, compared to that of cisplatin at 30.53 ± 0.23µM. Apoptotic promotion via the mitochondrial-dependent pathway was due to the elevation of intracellular reactive oxygen species (ROS), promotion of caspases, release of cytochrome c, fragmentation of DNA, and results of staining assay observed in all compound-treated cells. 2-4 are also capable of suppressing MCF-7 cell invasion and modulate Lys-48 also Lys-63 linked polyubiquitination, leading to proteasomal degradation. Analysis of gene expression via qRT-PCR revealed their modulation, which supported all activities conducted upon treatment with 2-4. Altogether, bismuth dithiocarbamate derivatives, with bismuth(III) as the metal center bound to ligands, isopropyl ethanol, pyrrolidine, and methyl ethanol dithiocarbamate, are potential anti-breast cancer agents that induce apoptosis and suppress metastasis. Further studies using other breast cancer cell lines and in vivo studies are recommended to clarify the anticancer effects of these compounds.

Synthesis and Characterization of Paclitaxel-Loaded Silver Nanoparticles: Evaluation of Cytotoxic Effects and Antimicrobial Activity.

Carrier system therapies based on combining cancer drugs with nanoparticles have been reported to control tumor growth and significantly reduce the side effects of cancer drugs. We thought that paclitaxel-loaded silver nanoparticles (AgNPs-PTX) were the right carrier to target cancer cells. We also carried out antimicrobial activity experiments as systems formed with nanoparticles have been shown to have antimicrobial activity. In our study, we used easy-to-synthesize and low-cost silver nanoparticles (AgNPs) with biocatalytic and photocatalytic advantages as drug carriers. We investigated the antiproliferative activities of silver nanoparticles synthesized by adding paclitaxel on MCF-7 (breast adenocarcinoma cell line), A549 (lung carcinoma cell line), C6 (brain glioma cell line) cells, and healthy WI-38 (fibroblast normal cell line) cell lines and their antimicrobial activities on 10 different microorganisms. The synthesized AgNPs and AgNPs-PTX were characterized by dynamic light scattering (DLS), scanning transmission electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, and X-ray spectroscopy. The nanoparticles were spherical in shape, with AgNPs ranging in size from 2.32 to 5.6 nm and AgNPs-PTXs from 24.36 to 58.77 nm. AgNPs demonstrated well stability of -47.3 mV, and AgNPs-PTX showed good stability of -25.4 mV. The antiproliferative effects of the synthesized nanoparticles were determined by XTT (tetrazolium dye; 2,3-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-tetrazolium-5-carboxanilide), and the proapoptotic effects were determined by annexin V/propidium iodide (PI) staining. The effect of AgNPs-PTX was more effective, and anticancer activity was higher than PTX in all cell lines. When selectivity indices were calculated, AgNPs-PTX was more selective in the A549 cell line (SI value 6.53 μg/mL). AgNPs-PTX was determined to increase apoptosis cells by inducing DNA fragmentation. To determine the antimicrobial activity, the MIC (minimum inhibitory concentration) test was performed using 8 different bacteria and 2 different fungi. Seven of the 10 microorganisms tested exhibited high antimicrobial activity according to the MIC ≤100 μg/mL standard, reaching MIC values below 100 μg/mL and 100 μg/mL for both AgNPs and AgNPs-PTX compared to reference sources. Compared to standard antibiotics, AgNPs-PTX was highly effective against 4 microorganisms.

Multiple SNPs Downregulate Gene Expression of Matrix Metallopeptidase 2 in MCF7 Breast Cancer Cells

Introduction: On a global scale, breast cancer contributes the highest cancer-related deaths in women due to metastasis which renders the treatments ineffective and non-targeted. The members of Matrix Metallopeptidases, particularly Matrix Metallopeptidase 2 (MMP2), are among the key players in breast cancer metastasis. In most cases, MMP2 was markedly upregulated and linked to poor prognosis. In a previous study, in silico analyses revealed that several coding single nucleotide polymorphisms (SNPs) of MMP2 were shown to reduce gene expression and mRNA stability of MMP2 in Malaysian breast cancer patients. Therefore, to validate the in silico predictions, the objective of this study was to determine the effects of multiple coding SNPs of MMP2 on the gene expression and mRNA stability of MMP2 in breast cancer cells. Methods: In the current study, breast adenocarcinoma MCF7 cells were transfected with MMP2 wild type and variant containing the coding SNPs. After confirmation of transfection by DNA sequencing, the gene expression level of MMP2 was evaluated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) whereas mRNA stability of MMP2 was determined following treatment with actinomycin D. Results: MMP2 wild type and variant were successfully transfected in MCF7 cells based on sequencing and PCR analysis. It was found that the presence of coding SNPs lowered the gene expression level of MMP2, but not the stability of MMP2 mRNA. Conclusion: This study supports the in silico effects of MMP2 coding SNPs on its gene expression in an in vitro model.

Exploring the broad-spectrum pharmacological activity of two less studied Australian native fruits: chemical characterisation using LCMS-driven metabolomics.

Australian fruits such as native currant (Acrotriche depressa) and lemon aspen (Acronychia acidula) are under-examined in terms of their therapeutic potential. In this study, the in vitro antiproliferative activity of native currant and lemon aspen extracts (water and ethanol) against MCF7 breast adenocarcinoma cells was determined using the Alamar blue assay. The most potent extracts (native currant water, NC-W; native currant ethanol, NC-Et; lemon aspen ethanol, LA-Et) were further evaluated using flow cytometry to detect the potential induction of apoptosis in MCF7 cells whereas 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay was implemented to understand the impact of the extracts on the intracellular reactive oxygen species (ROS) levels in MCF7 cells. Furthermore, the antioxidant activity of the extracts was assessed using ABTS [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate)], and CUPRAC (cupric reducing antioxidant capacity) assays. The antimicrobial susceptibility testing of NC-W, NC-Et, and LA-Et was carried out against Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli), and yeast (Candida albicans) strains using a resazurin-based assay. Additionally, potential metabolites in the NC-W and NC-Et extracts were analysed with liquid chromatography-mass spectrometry (LC-MS) driven metabolomics and chemometrics to spot differential and major metabolites. A dose-dependent antiproliferative activity was conferred by the NC extracts against MCF7 cells. Of the two LA extracts, only LA-Et showed a dose-dependent antiproliferative activity at higher concentrations. Both NC extracts and LA-Et induced apoptosis in MCF7 cells. None of the extracts increased the production of ROS significantly in MCF7 cells compared to the untreated control. A dose-dependent antioxidant activity was observed in both antioxidant assays. Both NC and LA extracts showed a similar minimum inhibitory concentration (MIC) value against S. aureus. Only LA-Et showed activity against E. coli, while NC-W and NC-Et were less active. All extracts showed MIC values of >1500 μg mL-1 against C. albicans. The metabolomics analysis revealed an abundance of flavonoids, fatty acyl derivatives, carbohydrates, carboxylic acids and their derivatives, and alkaloid compounds as potential bioactive metabolites in the NC extracts. In conclusion, both NC and LA showed antiproliferative (against MCF7 breast adenocarcinoma cells through the induction of apoptosis), strong antioxidant and minimal antimicrobial properties.

Comparison of antiproliferative effects of amlodipine and nebivolol against MCF-7 cells: An in vitro study

Background: Breast cancer (BC) has become the most common cancer among women in India. Both amlodipine, belonging to calcium channel blockers, and nebivolol, belonging to the beta blockers class have proven anticancer mechanisms. However, the effect has not been compared between these drugs till now. Aim and Objectives: The present study aims to compare the antiproliferation effects of amlodipine and nebivolol against human breast adenocarcinoma MCF-7 cells. Materials and Methods: Cell viability assay was used to screen the antiproliferation effects of the study drug molecules in MCF-7 cell cultures. The IC50 values were derived graphically by plotting the cell viability against drug concentration. Results: Both amlodipine and nebivolol exhibited dose-dependent cytotoxicity against BC cells. The IC50 of amlodipine was 166.6 μg/mL and nebivolol was 114.6 μg/mL. Conclusion: In this study, nebivolol showed potent cytotoxicity compared to amlodipine. This inference may provide further insights into future drug research.

Differences in nonoxidative sulfur metabolism between normal human breast MCF-12A and adenocarcinoma MCF-7 cell lines

Recent studies have revealed the role of endogenous hydrogen sulfide (H2S) in the development of breast cancer. The capacity of cells to generate H2S and the activity and expression of the main enzymes (cystathionine beta synthase; CBS, cystathionase γ-lyase; CGL, 3-mercaptopyruvate sulfurtransferase; MPST and thiosulfate sulfurtransferase; TST) involved in H2S metabolism were analyzed using an in vitro model of a non-tumourigenic breast cell line (MCF-12A) and a human breast adenocarcinoma cell line (MCF-7). In both cell lines, MPST, CGL, and TST expression was confirmed at the mRNA (RT-PCR) and the protein (Western Blot) level, while CBS expression was detected only in MCF-7 cells. Elevated levels of GSH, sulfane sulfur and increased CBS and TST activity were presented in the MCF-7 compared to the MCF-12A cells. It appears that cysteine might be mainly a substrate for GSH synthesis in breast adenocarcinoma. Increased capacity of the cells to generate H2S was shown for MCF-12A compared to MCF-7 cell line. Results suggest an important function of CBS in H2S metabolism in breast adenocarcinoma. The presented work may contribute to further research on new therapeutic possibilities for breast cancer - one of the most frequently diagnosed types of cancer among women.

Homeopathic dilutions of Phytolacca decandra induce cytotoxicity of human breast adenocarcinoma cells

Breast cancer is a malignant tumor frequently diagnosed in the female population that representsthe main cause of cancer death in women worldwide. Recently, the use of complementary therapiessuch as homeopathy has increased to alleviate the side effects of conventional allopathic treatments.However, the cellular and molecular effects of homeopathic medicaments have not been fullyclarified. Thus, the aim of this work was to evaluate the in vitro effects of Phytolacca decandrahomeopathic preparations on human breast adenocarcinoma cells. For this, MCF-7 breastadenocarcinoma cells were cultivated in the presence or absence of Phytolacca decandra mothertincture (PdTM) or centesimal Hahnemannian dilution (CH) of Phytolacca decandra: 30 or 200 CH.Determination of apoptosis and necrosis percentages, cytokine production and morphologicalchanges were evaluated after 24, 48 and 72 hours of culture in each of the treatments. Resultsobtained in cytotoxicity analyses showed a higher percentage of death in cells treated withhomeopathic dilutions, with similar results to that presented by cells treated with Doxorubicin orPdTM. In contrast, cells treated with homeopathic dilutions of Phytolacca decandra did not showmarked differences in the production of pro and anti-inflammatory cytokines when compared tountreated. Similarly, analyses of cell morphology did not display significant differences before andafter treatment with homeopathic dilutions, when compared to untreated cells. Already, cells treatedwith PdTM presented marked cellular alterations with observation of apoptotic bodies in the threeevaluated times. Together, results show that homeopathic dilutions of Phytolacca decandra inducedcytotoxicity of human breast adenocarcinoma cells in the absence of inflammatory process.