Breast Adenocarcinoma Research Articles

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.

Abstract PO5-27-06: Development of TTX-MC138, a First-In-Class miRNA-10b-Targeted Therapeutic Against Metastatic Cancers of Diverse Primary Disease Origins

Abstract Conventional therapies targeted towards the primary tumor cell oftentimes do not affect the metastatic cell and, in fact, may promote metastasis. For these reasons, our research has focused on developing therapies specific to unique properties of metastatic tumor cells. In our earlier work, we identified miRNA-10b as a master regulator of the viability of metastatic tumor cells. We determined that miRNA-10b not only promotes the capacity of tumor cells to migrate and invade surrounding tissue, but, importantly, serves as a powerful master regulator of the viability of cancer cells. This knowledge allowed us to develop a therapeutic miR-10b inhibitor, named TTX-MC138, which is effectively delivered to metastatic tumor cells and can elicit complete responses and life-long disease remissions in preclinical models of breast and pancreatic adenocarcinoma. As a critical step towards de-risking further clinical development of TTX-MC138, we have embarked on a Phase 0 clinical trial with Cu64-labeled TTX-MC138. The trial involves microdose injection of Cu64-labeled TTX-MC138 into stage IV breast cancer patients, followed by positron emission tomography-magnetic resonance imaging (PET-MRI). The study seeks to determine the pharmacokinetics of TTX-MC138 and its uptake in metastatic lesions. The impact of this work is three-fold. First it can establish that TTX-MC138, which is so effective in mice, will also accumulate in human metastases. This greatly de-risks the clinical development of the therapeutic because it shows drug delivery is indeed feasible. Second, the Phase 0 studies will reveal the pharmacokinetic behavior of TTX-MC138 which will allow one to establish dosing during therapy. Third, once TTX-MC138 reaches late-stage clinical trials, one can use the radiolabeled therapeutic to select patients for treatment, based on which patients’ metastases accumulate the drug. Studies that we present in support of the Phase 0 trial include dosimetry/PK and tissue distribution studies, as well as metabolite analysis in non-human primates. In non-human primates injected with Cu64-labeled TTX-MC138 at a dose of 100 microg, the organs with the highest uptake were the liver, heart, lung and spleen. The mean whole blood half-life was 12.2 ± 2.3 h (mean ± standard deviation) and the mean plasma blood half-life was 11.5 ± 1.8 h. RadioHPLC analysis of plasma samples showed that the drug is very stable with respect to metabolism. Combined, these studies support first-in-human testing of TTX-MC138 for the treatment of metastatic cancer and, by addressing the issue of drug delivery, enable the clinical development of a wide array of TTX-based therapeutics. Citation Format: Zdravka Medarova, Neil Robertson, Subrata Ghosh, Andreas Varkaris, Peter Caravan, Susan Duggan. Development of TTX-MC138, a First-In-Class miRNA-10b-Targeted Therapeutic Against Metastatic Cancers of Diverse Primary Disease Origins [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-06.

Abstract PO4-24-08: Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy

Abstract Introduction: Phyllodes tumors (PT) are rare fibroepithelial tumors of the breast, comprising ~1% of all breast cancers, a subset of which have considerable malignant potential. Malignant phyllodes tumors (MPTs) have aggressive biological behavior and high local and distant recurrence rates. Distant metastases of MPTs have a poor prognosis given the limited treatment options available. Surgery remains the primary treatment modality for these patients; however, initial investigations suggest a potential for targeted therapies in managing this disease. The identification of targetable opportunities and a comprehensive understanding of the mutational profiles of MPTs could greatly enhance treatment options. Therefore, we aimed to assess the molecular landscape of these tumors. Methods: Phyllodes tumor samples underwent molecular profiling at Caris Life Sciences through DNA (592-gene panel or whole exome) and RNA sequencing (whole transcriptome). The MPTs were classified into primary and metastatic based on the specimen biopsy site. PD-L1+ expression was tested by IHC (SP142; ≥2+, ≥5%). Tumor mutational burden (TMB)-High was defined as ≥10 mutation/Mb. Immune cell fractions in the tumor microenvironment (TME) were estimated using quanTIseq (Finotello, 2019). Mann-Whitney U, Chi-square, and Fisher-Exact tests were applied where appropriate. Results: We identified 57 analyzed MPTs, all from female patients, with a median age of 53 years (range: 19-88). Approximately half of samples (53%, n=30) were labeled as from primary breast sites, and the remaining sites were metastatic (47%, n= 27). Of metastatic sites, lung was the most common location (74.1%, n=20/27), followed by bone, sacrum, pancreas and small bowel. Alterations in MPT include TERT promoter (56.8%, n=21/37), MED12 (51.6%, n=16/31), TP53 (40.0%, n=22/55), and NF1 (31.8%, n=14/44) mutations, with less frequent mutations of EGFR (10.5%, n=6/57), PIK3CA (7.0%, n=4/57), and BRAF (3.5%, n=2/57). As compared to primary MPT, metastatic MPT had roughly 2-fold higher prevalence of NF1 (45.5%: n=10/22 vs 18.2% n=4/22, p=0.05), KMT2D (25.9%: n=7/27 vs 10.7%: n=3/28, p=0.18), and RB1 (25.0%: n=6/24 vs 9.5%: n=2/21, p=0.25) though not significant. Multiple gene mutations were observed exclusively in lung metastases, as compared to non-lung sites including: TERT promoter (64.3%: n=9/14 vs 0.0%, p=0.08), MED12 (60.0%: n=6/10 vs 0.0%, p =0.044), and RB1 (35.3%: n=6/17 vs 0.0%, p=0.01). Conversely, NF1 (43.8%: n=7/16 vs 50.0%: n=3/6, p=1.0) and KMT2D (20.0%: n=4/20 vs 42.9%: n=3/7, p=0.32) mutation prevalence was higher in other metastatic sites. PD-L1+ expression was observed in 13.3% (n=7) of MPT overall, with similar prevalence among local and metastatic sites. No dMMR/MSI-H was observed, while low LOH (those with genomic LOH in < 16% of segment analyzed) was seen across MPT. Compared to a large cohort of breast adenocarcinoma samples (n=9,926) representing both HER2+ and HER2- tumors, MPT had low ERBB2 expression comparable to HER2- samples. B cells, M2 macrophages and neutrophils had the highest median cell fractions in the TME of MPT. Additionally, one MPT sample harbored a pathogenic NTRK1 fusion (TPM4:NTRK1), and treatment with larotrectinib for over 16 months suggests a clinical response to therapy. Conclusions: Our study demonstrates the importance of employing next generation sequencing (NGS) in MPTs to detect actionable genomic alterations. To effectively analyze fusions, an NGS panel that include RNA sequencing is recommended, considering the occurrence of NTRK1 fusion reported herein. Although HER2 transcriptional expression was low, further investigations examining HER2 IHC in PTs are still necessary. These finding therefore highlight the importance of NGS in phyllodes tumors research, as it may uncover potential targeted treatment options for patients. Citation Format: Rani Bansal, Tolulope Adeyelu, Andrew Elliott, Antoinette Tan, Jane Meisel, Matthew Oberley, Stephanie Graff, Jorge Reis-Filho, George Sledge Jr, Sarah Sammons, Laura Rosenberger. Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-24-08.

Unveiling the anticancer potential of the ethanolic extract from Trichoderma asperelloides

Unveiling the anticancer potential of the ethanolic extract from Trichoderma asperelloides

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.

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.

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.

Silver ciprofloxacin (CIPAG): a multitargeted metallodrug in the development of breast cancer therapy.

The anti-proliferative activity of the known metalloantibiotic {[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O} (CIPAG) (CIPH = ciprofloxacin) against the human breast adenocarcinoma cancer cells MCF-7 (hormone dependent (HD)) and MDA-MB-231 (hormone independent (HI)) is evaluated. The in vitro toxicity and genotoxicity of the metalloantibiotic were estimated toward fetal lung fibroblast (MRC-5) cells. The molecular mechanism of the CIPAG activity against MCF-7 cells was clarified by the (i) cell morphology, (ii) cell cycle arrest, (iii) mitochondrial membrane permeabilization, and (iv) by the assessment of the possible differential effect of CIPAG on estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) transcriptional activation, applying luciferase reporter gene assay. Moreover, the ex vivo mechanism of CIPAG was clarified by its binding affinity toward calf thymus (CT-DNA).

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.

Differential osteo-specific invasion of patient-derived cancer cells in a microfluidic co-culture model

Cancer cell invasion to the surrounding extracellular matrix contributes to distant metastasis. There are no predictive models that focus on the accuracy of secondary site-infiltrative pattern. The degree of cancer invasion is regulated by receptive pre-metastatic niche. Herein, we show the feasibility of real time three-dimensional (3D) tissue-specific invasion of cancer stem like-cells (CSCs) from two different primary tumors employing a microfluidic device. An osteo-specific matrix (Osteomatrix-Collagen I, Os-Col) allows 3D osteogenic culture proven by differentiation of human adipose derived mesenchymal cells (ADSCs) into an osteoblastic lineage. In vitro enriched CSC-like cells (EpCAM+/CD44+/CD24− phenotype) derived from primary culture of oral squamous carcinoma and breast adenocarcinoma were used to demonstrate the differential strategy adopted for tumor progression. Morphological and viability parameters of the CSCs were monitored to assess the robustness as a realistic platform for in vitro osteotropic assay. Spatio-temporal elevated invasion into the osteo-specific matrix was evident in Os-Col compared to conventional collagen gel. Drug screening on co-cultures of CSC-like cells and osteoblasts exhibited drug resistance. Overall, this work demonstrates that the proposed microfluidic chip with bone-specific ECM can efficiently replicate in vitro biochemical conditions for distinguishing tissue-specific invasive phenotype and screening drug resistance. This may serve as a tool to systematically examine the contribution of the bone microenvironment on the progression of various primary cancers to predict its invasive form, advancing personalized therapies.

Triphenyltin(IV) compounds bearing modulated azo-carboxylato ligands: Synthesis, structural characterization, in vitro cytotoxicity, BSA/DNA binding affinity, and in silico studies

Three novel triphenyltin(IV) compounds with modulated azo-carboxylato ligands: triphenylstannyl (E)-4-((2-hydroxynaphthalen-1-yl)diazenyl)benzoate, 1, triphenylstannyl (E)-4-((4-hydroxyphenyl)diazenyl)benzoate, 2, and triphenylstannyl (E)-4-((4-(dimethylamino)phenyl)diazenyl)benzoate, 3, were synthesized and characterized by elemental analysis, FTIR and NMR (1H, 13C, 119Sn) spectroscopy. The structures and spectra of compounds were predicted by Density Functional Theory (DFT) methods at B3LYP-D3BJ/6-311++G(d,p)(H,C,N,O)/LanL2DZ(Sn) level of theory. Furthermore, the antitumor potential of ligand precursors, HL1–HL3, and appropriate organotin(IV) compounds 1–3 was evaluated across mouse melanoma B16F1, human breast adenocarcinoma MCF-7, human colorectal HT-29 and human prostate PC3 cell lines using MTT and CV assays. The organotin(IV) compounds exhibit enhanced cellular uptake and efficacy in reducing viable cell numbers when compared to free acids. Specifically, compound 3 demonstrates a notable impact at lower nanomolar concentrations on all tested cell lines. Moreover, 3 induces cell death in MCF-7 cells by inhibiting cell division and promoting the overproduction of cellular nitric oxide (NO), ultimately leading to caspase-independent apoptosis. Importantly, this process occurs without concurrent activation of autophagy or the generation of ROS/RNS species. The binding affinity of 1–3 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy and molecular docking simulations, suggesting their capacity to interact with these biomolecules.

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.

(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand.

The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the "piano stool" type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.

Comparative Assessment of Lignan Profiling and Biological Activities of Schisandra henryi Leaf and In Vitro PlantForm Bioreactor-Grown Culture Extracts.

This research's scope encompassed biotechnological, phytochemical, and biological studies of Schisandra henryi, including investigations into its in vitro microshoot culture grown in PlantForm bioreactors (temporary immersion systems, TISs), as well as extracts from leaves of the parent plant, focusing on anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The phytochemical analysis included the isolation and quantification of 17 compounds from dibenzocyclooctadiene, aryltetralin lignans, and neolignans using centrifugal partition chromatography (CPC), HPLC-DAD, and UHPLC-MS/MS tandem mass spectrometry with triple quadrupole mass filter methods. Higher contents of compounds were found in microshoots extracts (max. 543.99 mg/100 g DW). The major compound was schisantherin B both in the extracts from microshoots and the leaves (390.16 and 361.24 mg/100 g DW, respectively). The results of the anti-inflammatory activity in terms of the inhibition of COX-1, COX-2, sPLA2, and LOX-15 enzymes indicated that PlantForm microshoot extracts showed strong activity against COX-1 and COX-2 (for 177 mg/mL the inhibition percentage was 76% and 66%, respectively). The antioxidant potential assessed using FRAP, CUPRAC, and DPPH assays showed that extracts from microshoot cultures had 5.6, 3.8, and 3.3 times higher power compared to extracts from the leaves of the parent plant, respectively. The total polyphenol content (TPC) was 4.1 times higher in extracts from the in vitro culture compared to the leaves. The antiproliferative activity against T-cell lymphoblast line Jurkat, breast adenocarcinoma cultures (MCF-7), colon adenocarcinoma (HT-29), and cervical adenocarcinoma (HeLa), showed that both extracts have considerable effects on the tested cell lines. The antimicrobial activity tested against strains of Gram-positive and Gram-negative bacteria and fungi showed the highest activity towards H. pylori (MIC and MBC 0.625 mg/mL).

Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts

AimsTo clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma.MethodsImmunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and CLDN18...

Pulsed voltage cold atmospheric plasma jet and gold nanoparticles enhance cytotoxic anticancer effect

Efficient and biologically safe mode of cold atmospheric plasma jet (CAPJ) is crucial for the development of CAPJ-based anticancer therapy. In the experiment and numerical simulations, by changing the pulse duration of a positive-pulsed (PP) voltage, we found the optimal CAPJ modes with a regular streamer propagation and a maximum discharge current at a temperature T< 42 ∘C. These CAPJs substantially suppressed the viability of cancer cells. To enhance a cytotoxic effect of CAPJ treatment, gold nanoparticles (NPs) were added to the cells before and after the CAPJ exposure. Combination of CAPJ, generated with the PP voltage, and gold NPs decreased the viability of NCI-H23 epithelial-like lung adenocarcinoma, A549 lung adenocarcinoma, BrCCh4e-134 breast adenocarcinoma and uMel1 uveal melanoma cells. Polyethylene glycol-modified NPs with attached fluorescent labels were used to visualize the uptake of NPs. We demonstrated that NPs efficiently entered the cells when were added to the cells just before CAPJ exposure or up to two hours afterwards. The efficiency of NPs penetration into cells positively correlated with the induced cytotoxic effect: it was maximal when NPs was added to cells right before or immediately after CAPJ exposure. Summarizing, the treatment with optimal CAPJ modes in combination with modified NPs, bearing the cancer-addressed molecules and therapeutics may be the next strategy of strengthening the CAPJ-based antitumor approaches.

The non-steroidal anti-inflammatory drugs based on Zinc(II) picoline complexes: Synthesis, characterization, and evaluation of antiproliferative effects against human breast adenocarcinoma MDA-MB-453 cells by inducing ROS-mediated apoptosis and down-regulating PI3K/AKT signaling pathway

This work aims to synthesize zinc(II) non-steroidal anti-inflammatory complexes and to evaluate their anticancer abilities on different cancer cell lines. In this context, four new zinc(II) complexes including the NSAIDs mefenamic acid or niflumic acid and picoline derivatives {[Zn2(μ-mef)3(3-pic)2] 1, [Zn3(μ-mef)6(2-pic)2] 2, [Zn3(μ-mef)6(4-pic)2] 3 and [Zn(nif)2(4-pic)2]} 4 were synthesized. The molecular structures were identified by elemental analysis, FT-IR, 1H NMR (complexes 2 and 3), UV–Vis, thermal analysis, and X-ray diffraction (complexes 1 and 4), indicating that one complex was mononuclear, one complex was binuclear, and two complexes were trinuclear. The deprotonated mefenamato ligands bind to the zinc(II) ion via carboxylate oxygen atoms and chelate in a bridging bidentate asymmetric form. The deprotonated niflumato ligand acts as a monodentate ligand. UV–Vis spectroscopy was used to assess the complexes' stability. The stoichiometry of the synthesized complexes was determined by 1H NMR and thermal studies. XTT assays showed that all complexes exhibited dose-dependent antiproliferative effects against breast cancer MCF-7 and MDA-MB-453 cells, colon cancer HT-29 cells, and lung cancer A549 cells. The highest cytotoxicity was exhibited by complex 3 against MDA-MB-453 cells with an IC50 value of 8.28 µM. The mechanistic studies performed by flow cytometry revealed that complex 3 exerted its in vitro anticancer activity against MDA-MB-43 cells by inducing apoptosis, increasing ROS production, and inhibiting the PI3K/AKT signaling pathway.