Human Breast Adenocarcinoma Cell Research Articles

Enzymatic synthesis of biocompatible polypyrrole with enhanced electrochemical properties for supercapacitors

This study focuses on the biocompatible and ecofriendly enzymatic synthesis of conductive polypyrrole (PPy) using mediators for supercapacitor electrode material. The work investigates the effects of various mediator systems on laccase-catalyzed oxidation of pyrrole and is confirmed through Fourier transform infrared spectroscopy (FTIR) and Ultraviolet (UV) visible spectroscopy. The x-ray diffraction (XRD) and transmission electron microscopy (TEM) analysis has revealed that both mediators and laccase can produce crystalline and amorphous PPy with agglomeration of globular-shaped particles. The PPy-ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) demonstrates higher decomposition temperatures, indicating superior thermal stability up to 400 °C. Electrochemical studies such as cyclic voltammetry (CV), galvanometric charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS) revealed that PPy-ABTS possesses good electrochemical properties. Compared to other laccase-mediated materials synthesized PPy in this study, PPy-ABTS exhibits higher specific capacitance values (242 F g−1 by CV at 10 mV s−1 and 153 F g−1 by GCD at 1 A g−1), with a capacitance retention of nearly 90 % after 10000 cycles. Cytotoxicity study shows that PPy-ABTS has an IC50 value of 528 μg ml−1 against human breast adenocarcinoma (MCF-7) cells, indicating its biocompatibility. Consequently, PPy-ABTS emerges as a promising electrode material for high-performance supercapacitors. Its unreported biocompatibility opens up possibilities for diverse biomedical applications.

Anabasis articulata (Forssk.) Moq. food aqueous extract triggers oxidative stress-induced senescence and reduces metastatic power in MDA-MB-231 cells

Ancient ethnobotanical practices handed down through traditional knowledge are still commonly employed to treat various pathologies, although the scientific reasons underlying their biological effects have not been clarified yet. In this contribution, the potential antitumoral activity of the aqueous extract from A. articulata (AAE) was investigated to validate the hypothesis of the Algerian folk medicine which would suggest this plant derivative as a functional food for treating breast cancer. A. articulata phytocomplex, isolated by maceration following exactly the African recipe, has been already characterized by our research group in previous works. Thus, the antiproliferative function of AAE against MDA-MB-231, a highly aggressive human breast adenocarcinoma cell line, was evaluated. Slowing down of cell growth, absence of cytotoxicity and DNA fragmentation, and cell cycle arrest at the G2/M phase were observed after treatment with AAE at different doses (0.3–6 mg of dried plant material equivalent per mL of culture medium) for 24 and 48 h. Wound and transwell assays proved that AAE possessed both antimigration and antiinvasive capacities, evidence also supported by molecular analyses focused on Metalloproteases (MMP-2 and MMP-9), Vimentin and ανβ3-Integrin. These results, together with the demonstration of the activation of p53/p21WAF1/Cip1/p27Kip1 pathway and the increase of oxygen reactive species levels, suggested that AAE triggered a senescence process. The final confirmation was obtained by a specific kit staining senescent cells. All our data would explain the efficacy of the Algerian medicinal remedy based on the intake of the investigated functional plant food and would highlight the basics for developing novel natural pharmacological products based on AAE and showing preventive and therapeutic antineoplastic potentialities against highly aggressive breast cancers.

Ru(II)-Arene Complexes of Curcumin and Bisdesmethoxycurcumin Metabolites.

Curcuminoids and their complexes continue to attract attention in medicinal chemistry, but little attention has been given to their metabolic derivatives. Here, the first examples of (arene)Ru(II) complexes with curcuminoid metabolites, tetrahydrocurcumin (THcurcH), and tetrahydrobisdesmethoxycurcumin (THbdcurcH) were prepared and characterized. The neutral complexes [Ru(arene)(THcurc)Cl] and [Ru(arene)(THbdcurc)Cl] (arene = cymene, benzene, or hexamethylbenzene) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structures of the three complexes were determined by X-ray diffraction analysis. Compared to curcuminoids, these metabolites lose their conjugated double bond system responsible for their planarity, showing unique closed conformation structures. Both closed and open conformations have been analyzed and rationalized by using density functional theory (DFT). The cytotoxicity of the complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), human breast adenocarcinoma cells (MCF-7 and MCF-7CR), as well as against non-tumorigenic human embryonic kidney cells (HEK293) and human breast (MCF-10A) cells and compared to the free ligands, cisplatin, and RAPTA-C. There is a correlation between cellular uptake and the cytotoxicity of the compounds, suggesting that cellular uptake and binding to nuclear DNA may be the major pathway for cytotoxicity. However, the levels of complex binding to DNA do not strictly correlate with the cytotoxic potency, indicating that other mechanisms are also involved. In addition, treatment of MCF-7 cells with [Ru(cym)(THcurc)Cl] showed a significant decrease in p62 protein levels, which is generally assumed as a noncisplatin-like mechanism of action involving autophagy. Hence, a cisplatin- and a noncisplatin-like concerted mechanism of action, involving both apoptosis and autophagy, is possible.

Polycaprolactone Microsphere‐Encapsulated Fluconazole‐Loaded Zinc Oxide and Hydroxyapatite Nanocomposites for Enhanced Biological Performance

AbstractOsteomyelitis (OM), a debilitating disease caused by a microbial infection of the bones, continues to pose a formidable obstacle for orthopedic surgeons. The conventional methods for the prevention and treatment of OM are insufficient. In this research work, we developed a strategic green nanostructure using the antifungal drug Fluconazole (FCZ)‐assimilated zinc oxide nanoparticles (ZnO‐NPs) and hydroxyapatite (HAp) nanostructures as filler and hydrophobic polycaprolactone (PCL) as matrix by a solution‐based chemical method. The ceramic carrier‐like nanostructures ZnO and HAp were synthesized by the in situ precipitation method. The physicochemical characterization of the prepared polymer‐coated drug ceramic nanocomposite (FCZ‐ZnO‐HAp‐PCL) was achieved using Fourier transform infrared spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), particle size distribution (PSD), X‐ray diffraction (XRD), and Energy‐dispersive X‐ray (EDX) analysis. Furthermore, the biocompatibility and anticancer activity of the nanocomposite were explored by an MTT assay study. Successfully synthesized FCZ‐ZnO‐HAp‐PCL nanocomposite exhibited profound antimicrobial activity against targeted microbe species and potential cytotoxicity towards MCF‐7 human breast adenocarcinoma cell lines, which may be potentially used for the treatment of OM and prospective infections.

Controlled dual activity of an organometallic antibiotic through micelle formulation

Sodium Lauryl Sulphate (SLS) and Cetyltrimethylammonium bromide (CTAB) were employed to create micelles (SLS@CIPTIN and CTAB@CIPTIN) of the organometallic antibiotic Ph2Sn(CIP)2 (CIPTIN) (where HCIP= ciprofloxacin). The characterization of the micelles was conducted in the solid-state using melting point, Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR), 119Sn Mössbauer and X-ray Fluorescence (XRF) spectroscopies, and Thermogravimetry/Differential Thermal Analysis (TG-DTA), while in solution, by Ultra violet-Visible (UV–Vis) and Nucleus Magnetic Resonance (1HNMR ) spectroscopic techniques were employed. The compounds were tested for their antiproliferative activity against human breast adenocarcinoma cells: MCF-7 (hormone depended (HD)) and MDA-MB-231 (hormone independent (HI)). The in vitro and in vivo non-genotoxicity was confirmed with micronucleus (MN) and Artemia salina assay. The antiproliferative mechanism of action of SLS@CIPTIN and CTAB@CIPTIN was studied by cell morphology and cell cycle arrest. The antibacterial activity was evaluated using Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZ) against Minimum Bactericidal Concentration (MBC) against Gram-negative strains P. aeruginosa, E. coli, as well as Gram-positive strains S. epidermidis and S. aureus. The results indicate that both the investigated CIPTIN and its supramolecular assembly (SLS@CIPTIN) exhibit activity. Therefore, the encapsulation of antimicrobial compounds can indeed be regarded as an attractive strategy for the development of new dual-active agents. These agents offer concurrent anticancer and antibacterial attributes without inducing toxicity.

Abstract LB430: Identification of therapeutic target in breast cancer using G-quadruplex binding ligands

Abstract G-quadruplex (G4) motifs are noncanonical nucleic acid structures formed from staked guanine rich tetrads. G4 motifs have been shown to play significant effects on gene expression in all domains of life and are predominantly enriched in the regulatory regions such as promoters and enhancers of the human genome. G4-ligand mediated stabilization or destabilization of G4 structures has been discussed as a potential therapeutic strategy against tumor cells. However, the structure-specificity of G4-binding ligands remains a considerable challenge in determining the target-specificity. Therefore, it is necessary to understand the global effects of such G4-binding ligands at the transcriptome level to identify novel target(s) based on molecular structures and binding modes of both G4 motifs and ligands. In this study, we reported a top-down approach to extrapolate transcriptome-wide effects of two eminent G4-binding ligands Quarfloxin and Pyridostatin in human breast adenocarcinoma (MCF7) cell lines by RNA-seq analysis. Quadparser analysis was performed to analyze putative G4 forming sequences in protein coding breast cancer genes promoters. RNA-seq data was combined with Quadparser analysis to reveal that over 85% of the differentially expressed genes in both Pyridostatin and Quarfloxin contained G4 forming sequences in promoter region. Gene ontology analysis showed that both ligands affected key genes involved in extracellular matrix (ECM), architecture and cellular functions. A notable tumor suppressor deubiquitinase (DUBs) Cylindromatosis (CYLD) gene expression was particularly increased with Pyridostatin compared to Quarfloxin. In vitro assays also confirmed an increase in CYLD expression by qRT-PCR and Western blot. The detailed molecular mechanism of G4-mediated increase in CYLD expression is under study. Collectively, the current results present a new approach to identify G4-ligands binding target in breast cancer cells and provide insights into designing G4-ligands as an anti-cancer therapeutics. Citation Format: Maria Razzaq, Subramaniyam Ravichandran, Nazia Parveen, Kyeong Kyu Kim. Identification of therapeutic target in breast cancer using G-quadruplex binding ligands [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB430.

In Vitro Antiviral and Anticancer Effects of Tanacetum sinaicum Essential Oil on Human Cervical and Breast Cancer.

Cervical cancer has been linked to human papillomavirus (HPV) types 16 and 18. Essential oils (EOs) are vital natural products of plants with various therapeutic and biological properties. The purpose of this study is to investigate and assess Tanacetum sinaicum essential oil's possible antiviral and anticancer properties, with a focus on its in vitro effects on human cervical cancer and human breast adenocarcinoma cell lines. Tanacetum sinaicum EO was extracted via hydrodistillation (HD) and characterized using gas chromatography-mass spectrometry (GC-MS). MTT assay was used to determine the cell viability of Hela (a human epithelial cervical cancer) and MCF-7 (human breast adenocarcinoma) cell lines. Quantitative real-time polymerase chain reaction (PCR) was utilized to assess the antiviral efficacy of EO against HPV-16 and 18, and anti-metastatic characteristics. The biological activity of EO was assessed using Autophage and Cell genotoxicity via the comet assay. EO is mostly composed of chrysanthenyl acetate, thujone, and verbenol. The cell viability was reduced after 24 hours of incubation at doses from 100 to 400 µg/ml. Concentrations of 800 to 3,200 µg/ml significantly inhibit cell growth. After a 24-hour incubation period, doses ranging from 100 to 400 µg/ml reduced cell viability from 62 to 72%. Concentrations of 800 to 3,200 µg/ml significantly suppress cell growth by over 95%. In MCF7 and HeLa cell lines, EO lowered virus copy numbers in a dose-dependent manner, with higher concentrations of the oil inhibiting virus replication more effectively. EO treatment increased the number of autophagosomes/autolysosomes and acidic vesicular organelles in both cell lines. On the HeLa and MCF7 cell lines, EO demonstrated antiproliferative and antimetastatic effects. The results demonstrated that EO had dose-dependent genotoxic effects on both cancer cell lines, as evidenced by DNA damage. Tanacetum sinaicum EO is a prospective source of natural bioactive compounds that can be employed in pharmaceutical and medicinal applications due to its antiviral, antiproliferative, anti-metastatic and genotoxic properties.

Design, Synthesis and In-Silico Studies of Piperidine-Dihydropyridine Hybrids as Anticancer Agents.

In this study, we designed, synthesized and characterized a novel series of piperidine-dihydropyridine hybrid compounds and characterized them by 1 H-NMR, 13 C NMR, mass spectrometry (MS), and elemental analysis. Subsequently, we assessed their in vitro anticancer potentials against the human breast adenocarcinoma cell line MCF-7 and the lung cancer cell line A-549. Several of these compounds demonstrated significant activity, with IC50 values ranging from 15.94 μM to 48.04 μM for A-549 and 24.68 μM to 59.12 μM for MCF-7, when compared to the reference drug Cisplatin.Notably, a compound featuring a 3-fluoro substitution in the carboxamide series exhibited robust inhibitory effects, with an IC50 of 15.94±0.201 μM against A-549 cells and an IC50 of 22.12±0.213 μM against MCF-7 cells, respectively. Additionally, a compound containing a cyclobutyl ring displayed potent activity, with an IC50 of 16.56±0.125 μM against A-549 and an IC50 of 24.68±0.217 μM against MCF-7 cells, respectively. Furthermore, molecular docking studies against the Epidermal Growth Factor Receptor (EGFR) (PDB ID: 2J6M) revealed favourable binding scores and interactions, suggesting their potential as promising candidates for further investigation in the context of anticancer drug development.

Proapoptotic effects of ceranib-2 in combination with radiation therapy on human breast cancer cells.

Strategies for cancer therapy involve radiation therapy (RT), which accounts for about 40% of all cancer treatment types. As to current chemotherapeutics, cancer cells also develop resistance that remains a clinical problem, such as disease recurrence. Recent studies focused on understanding the molecular mechanisms of radiation-induced cell death. Conventional RT aims at treatment with a single fraction per day of 8-30 Gy per fraction. Radiotherapy increases intracellular ceramide levels that trigger cell death. Additionally, increasing intracellular ceramide by radiation may restore therapeutic sensitivity to cancer treatments. Drugs that inhibit ceramide-metabolizing enzymes like ceramidases are expected to be radiotherapy sensitizers. In this research, we investigated the proapoptotic effects of SRS alone and in combination with ceranib-2, a ceramidase inhibitor in human breast adenocarcinoma cells. The molecular mechanism of action of RT and ceranib-2 was investigated on MCF-7 cells exposed to 13 µM ceranib-2 for 24 hours following 20 Gy radiation using MTT, radiotherapy, and annexin-V analyses. Results indicated that the dose of 20 Gy radiation induces apoptosis on human breast cancer cells with and without co-treatment with ceranib-2 by causing cytotoxicity in the cells. Based on the results of ceranib-2 exposure, it can be concluded that the mechanism of action may rely on an increase of intracellular ceramides, also called apoptotic lipids. The study results suggest that co-treatment of human breast adenocarcinoma cells with a ceramidase inhibitor, ceranib-2, and a high dose of radiation of 20 Gy exerted cytotoxicity and apoptosis and might be a solid, potent alternative to current therapy strategies.

Facile and Eco-Friendly Synthesis of Silver Nanoparticles using Semecarpus anacardium and their Antibacterial and Anticancer Activity

Plant extracts are utilized to synthesize nanoparticles containing bioactive compounds that can effectively decrease metal toxicity. In present study, the aqueous extracts of Semecarpus anacardium leaves and stems were used to reduce silver nitrate and synthesize silver nanoparticles (AgNPs), which have potent antibacterial and anticancer effects. The physico-chemical methods such as XRD, UV-Vis, Fourier transform IR and SEM were used to characterize the biogenci silver nanoparticles. These methods validated the synthesis of AgNPs with smaller size and homogeneously sphere-shaped AgNPs (10-50 nm) after incubation with S. anacardium leaf and stem extract. Stem extract derived AgNPs showed the significant cancer fighting abilities in the human breast (MDA-MB-231) and prostate adenocarcinoma (PC-3) cells compared to that of derived AgNPs. Stem extract derived AgNPs exhibits the significant antibacterial activity against E. coli and B. subtilis with respect to the gentamycin. Additionally, the study demonstrated that green synthetic AgNPs may be investigated for use as a treatment against bacterial infections.

Conjugation of an anti-metabolite nucleobase analogue with a mitochondriotropic agent via palladium(II) against breast cancer cells

The conjugation of the uracil (a nucleobase) analogue, 6-methyl-thiouracil (MTUC), with the mitochondriotropic agent of Tri-o-Tolyl-Phosphine (TOTP) through palladium(II) leads to the formation of the metallodrug of formula [PdCl(TOTP)(MTUC)] (1). The metallodrug was characterized in solid state using Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy and X-ray diffraction crystallography (XRD), while its behavior in solution was examined through Ultra Violet (UV) and 1H NMR spectroscopies. The in vitro cytotoxicity of 1 was assessed against human breast adenocarcinoma cell lines: MCF-7 (hormone-dependent (HD)) and MDA-MB-231 (hormone-independent (HI)), as well as fetal lung fibroblast (MRC-5) cells. The MCF-7 cell morphology suggests apoptotic pathway, and this was confirmed by Acridine Orange/Ethidium Bromide (AO/EB) Staining, and the loss of the permeabilization of the mitochondrial membrane. The binding affinity of 1 toward the calf thymus (CT) DNA was clarified.

Comparative Solution Equilibrium Studies on Anticancer Estradiol-Based Conjugates and Their Copper Complexes

Steroids are often considered valuable molecular tools for the development of anticancer agents with improved pharmacological properties. Conjugation of metal chelating moieties with a lipophilic sterane backbone is a viable option to obtain novel anticancer compounds. In this work, two estradiol-based hybrid molecules (PMA-E2 and DMA-E2) with an (N,N,O) binding motif and their Cu(II) complexes were developed. The lipophilicity, solubility, and acid-base properties of the novel ligands were determined by the combined use of UV-visible spectrophotometry, pH-potentiometry, and 1H NMR spectroscopy. The solution speciation and redox activity of the Cu(II) complexes were also investigated by means of UV-visible and electron paramagnetic resonance spectroscopy. Two structurally analogous ligands (PMAP and DMAP) were also included in the studies for better interpretation of the solution chemical data obtained. Three pKa values were determined for all ligands, revealing the order of the deprotonation steps: pyridinium-NH+ or NH(CH3)2+, secondary NH2+, and OH. The dimethylamine derivatives (DMA-E2, DMAP) are found in their H2L+ forms in solution at pH 7.4, whereas the fraction of the neutral HL species is significant (34–37%) in the case of the pyridine nitrogen-containing derivatives (PMA-E2, PMAP). Both estradiol derivatives were moderately cytotoxic in human breast (MCF-7) and colon adenocarcinoma (Colo-205) cells (IC50 = 30–63 μM). They form highly stable complexes with Cu(II) ions capable of oxidizing ascorbate and glutathione. These Cu(II) complexes are somewhat more cytotoxic (IC50 = 15–45 μM) than their corresponding ligands and show a better selectivity profile.

New Imidazo[4,5‐c]pyridine‐piperidine Hybrids as Potential Anti‐cancer Agents and In‐Silico Studies

AbstractDesign and synthesis of a series of novel hybrid molecules that combine Imidazo[4,5‐c] pyridines with piperdines are presented in this paper. Total 17 derivatives were meticulously synthesized and characterized using 1H NMR, 13C NMR, MS and elemental analysis techniques. The in vitroanticancer activities are estimated by verifying their effectiveness against the MCF‐7 human breast adenocarcinoma and A549 lung cancer cell line, with cisplatin and doxorubicin serving as reference drugs. Several of these compounds demonstrated significant potential, displaying IC50 values within the range of 12.26–84.5 μM for A549, and 13.37–69.82 μM for MCF‐7. Notably, compound 11 bis found to be more potent than the standard drug cisplatin with an IC50 of 12.26±0.8 μM against A549 cells, while compound 11 d exhibited highest inhibition with an IC50 of 13.37±0.4 μM against MCF‐7 cells. Although its effectiveness was moderately lower when compared to doxorubicin, it still retained substantial anticancer activity. Molecular docking studies were performed to decouple the binding affinity and ligand interactions of the compounds with the estrogen receptor alpha (ERα) (PDB ID: 3ERT). The pharmacokinetic evaluation revealed favourable drug‐likeness properties for all the molecules, suggesting their potential as therapeutic agents.

Oxidation-derived anticancer potential of sumanene-ferrocene conjugates.

An effective synthetic protocol towards the oxidation of sumanene-ferrocene conjugates bearing one to four ferrocene moieties has been established. The oxidation protocol was based on the transformation of FeII from ferrocene to FeIII-containing ferrocenium cations by means of the treatment of the title organometallic buckybowls with a mild oxidant. Successful isolation of these ferrocenium-tethered sumanene derivatives 5-7 gave rise to the biological evaluation of the first, buckybowl-based anticancer agents, as elucidated by in vitro assays with human breast adenocarcinoma cells (MDA-MB-231) and embryotoxicity trials in zebrafish embryos supported with in silico toxicology studies. The designed ferrocenium-tethered sumanene derivatives featured attractive properties in terms of their use in cancer treatments in humans. The tetra-ferrocenium sumanene derivative 7 featured especially beneficial biological features, elucidated by low (<40% for 10 μM) viabilities of MDA-MB-231 cancer cells together with a 1.4-1.7-fold higher viability of normal cells (human mammary fibroblasts, HMF) for respective concentrations. Compound 7 featured significant cytotoxicity against cancer cells thanks to the presence of sumanene and ferrocenium moieties; the latter motif also provided the selectivity of anticancer action. The biological properties of 7 were also improved in comparison with those of native building blocks, which suggested the effects of the presence of the sumanene skeleton towards the anticancer action of this molecule. Ferrocenium-tethered sumanene derivatives exhibited potential towards the generation of reactive oxygen species (ROS), responsible for biological damage to the cancer cells, with the most efficient generation of the tetra-ferrocenium sumanene derivative 7. Derivative 7 also did not show any embryotoxicity in zebrafish embryos at the tested concentrations, which supports its potential as an effective and cancer-specific anticancer agent. In silico computational analysis also showed no chromosomal aberrations and no mutation with AMES tests for the compound 7 tested with and without microsomal rat liver fractions, which supports its further use as a potent drug candidate in detailed anticancer studies.

Quaternary nanorods: promising versatile agents for cancer therapy, antimicrobial strategies and free radical neutralization

Cu2XSnS4 (CXTS; X: Zn, Mn or Co) nanorods (NRs) were prepared by a simple hot-injection method and their cytotoxic activities on human breast adenocarcinoma (MCF-7), metastatic melanoma (451Lu) and embryonic kidney (HEK-293) cell lines were investigated for the first time. The antibacterial activities of these nanoparticles on both gram-positive (S. aureus) and gram-negative (E. coli) pathogenic bacteria as well as their DPPH (2,2-diphenyl-1- picrylhydrazyl) scavenging activities were evaluated. The structural characterizations show that the obtained nanoparticles have the same crystal structure and are shaped as nanorods with an average 10–40 nm edge length. The data obtained in cytotoxicity studies revealed that the synthesized CXTS NRs have a significant inhibition effect, especially on cancer cell lines (MCF-7 and 451Lu), in a dose-dependent manner over a period of 24 h, demonstrating their potential for use as anticancer agents. In addition, the findings indicate that the synthesized nanorods possess strong antibacterial properties against the pathogenic microorganisms tested and display a marked antioxidant effect through efficient elimination of DPPH activity. This comprehensive study sheds light on the creation and development of CXTS NRs as promising versatile agents in various biomedical and environmental applications such as cancer therapy, antimicrobial strategies and the neutralization of free radicals.

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.

Synthesis, spectroscopic elucidation, density functional theory calculation, and molecular docking studies of a novel series of tetradentate macrocyclic Schiff base ligands and their Zn(II) complexes and investigations of their antimicrobial, anti‐inflammatory, and anticancer activities

In the present work, novel Schiff base macrocyclic Zn(II) complexes [Zn(N8O4MacL1)Cl2–Zn(N8O4MacL3)Cl2] were synthesized by the reaction of ZnCl2 and macrocyclic ligands (N8O4MacL1–N8O4MacL3) derived from the condensation of ligand (L) and dicarboxylic acids [HOOC‐(CH2)n‐COOH]. The structural confirmation of the newly synthesized compounds was accomplished through various analytical techniques, including elemental analysis, infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), UV–visible spectroscopy, and powder X‐ray diffraction (XRD) studies. The spectral data provided evidence that the macrocyclic ligands acted as tetradentate ligands, forming coordination bonds with Zn(II) ions through the nitrogen atom of the imine (&gt;C=N) group. The coordination complexes exhibited an octahedral geometry around the zinc ion, with two chloro groups covalently attached. Density functional theory (DFT) studies of the synthesized Schiff base macrocyclic compounds were carried out to determine their structural and electronic properties. The antimicrobial potential of the macrocyclic compounds was examined against a panel of pathogenic microbes, including four bacterial strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Xanthomonas campestris) and two fungal strains (Fusarium oxysporum and Candida albicans). Then, the newly synthesized Schiff based macrocyclic compounds were evaluated for their anti‐inflammatory activity using an egg albumin method. The synthesized compounds were subjected to further evaluation to assess their potential as anticancer agents against MCF‐7 (human breast adenocarcinoma cell line), HCT‐116 (human colon cancer cell line), and A549 (human alveolar adenocarcinoma epithelial cell line). In addition, molecular docking studies were conducted to explore the potential interactions between the synthesized compounds and the target proteins VEGFR2 (PDB ID 1YWN), EGFR (PDB ID 1M17), and DNA gyrase B (PDB ID 4URO). It was found that there was a high correlation between the experimental results and the docking calculations.

Herbal Melanin Inhibits Real-Time Cell Proliferation, Downregulates Anti-Apoptotic Proteins and Upregulates Pro-Apoptotic p53 Expression in MDA-MB-231 and HCT-116 Cancer Cell Lines.

Background and Objectives: Cancer is the second-most-important deadly disease in the world, leading to severe socioeconomic consequences and posing a public threat. Consequently, breast and colorectal cancers are significant cancer types that affect women and men more commonly, respectively. Treatment failure or recurrent diseases frequently occur due to resistance, in addition to the side effects of the currently available anticancer agents. Therefore, in this study, herbal melanin anticancer activity was investigated against human breast adenocarcinoma (MDA-MB-231) and human colorectal (HCT 116) cell proliferation and the expression of downregulated anti-apoptotic proteins and upregulated pro-apoptotic p53. Materials and Methods: MDA-MB-231 and HCT 116 cells were monitored for their real-time proliferation properties using Xcelligence. Herbal melanin of various concentrations significantly inhibited MDA-MB-231 and HCT 116 cell proliferation. Then, the expression of proapoptotic and anti-apoptotic proteins such as p53, Bcl-2 and Bcl-xl was studied using Western blotting. Results: The Bcl-2 and Bcl-xl expressions were downregulated, while the p53 expression was upregulated after treatment with herbal melanin. Similarly, the expression of apoptotic proteins such as Bcl-2, Bcl-xl, XIAP, Survivin, Bid, Bax, p53, Cytochrome C, PARP genes and mRNA was studied after herbal melanin treatment using real-time PCR, which revealed the downregulation of Bcl-2, Bcl-xl, XIAP and Survivin and the upregulation of Bid, Bax, p53, Cytochrome C and PARP apoptotic protein expression. Also, caspase 3 and 9 expressions were monitored after the treatment with herbal melanin, which revealed the upregulation of both the MDA-MB-231 and HCT 116 cell types. Conclusions: Overall, herbal melanin can be used as an alternative anticancer agent against the MDA-MB-231 and HCT 116 cell types.

Curcumin-loaded albumin submicron particles with potential as a cancer therapy: an in vitro study.

Curcumin (CUR), a polyphenolic compound, shows promising biological properties, particularly antioxidant activity. However, its medical applications are limited due to its low water solubility, bioavailability, and pH-instability. CUR-loaded albumin microparticles (CUR-HSA-MPs) of submicron size in the range of 800 to 900 nm and a zeta potential of -15 mV were prepared. The CUR loading efficiency was up to 65%. A maximum release of 37% of the encapsulated CUR was observed within 6 h when the CUR-HSA-MPs were dispersed in 50% ethanol in PBS at pH 7, while in RPMI 1640 medium the release was 7%. This demonstrates a sustainable release. The in vitro cytotoxicity of CUR-HSA-MPs showed promising anticancer potential against human hepatocellular carcinoma (Huh-7) and human breast adenocarcinoma (MCF-7) cell lines, although this effect was less pronounced in human dermal fibroblasts (HDFB) and human cholangiocyte (MMN) cell lines. Confocal microscopy was used to confirm the uptake of CUR-HSA-MPs by cancer cells. Our studies revealed that HSA-MPs are potentially promising vehicles for increasing the solubility and bioavailability of CUR.