Healthy Cell Lines Research Articles

Chemical Profile of Kumquat (Citrus japonica var. margarita) Essential Oil, In Vitro Digestion, and Biological Activity

Kumquat is one of the smallest citrus fruits (from the Rutaceae family), and its essential oil’s biological effects have not yet been sufficiently researched, in contrast to the essential oils of its relatives. Therefore, the aim of this large-scale study was to investigate the chemical profile of kumquat essential oils (KEOs) isolated by microwave-assisted distillation (MAD) and Clevenger hydrodistillation using GC-MS analysis. To test the bioaccessibility of their bioactive components, in vitro digestion with commercially available enzymes was performed. The final step of this research was to test their cytotoxic activity against a cervical cancer cell line (HeLa), a human colon cancer cell line (HCT116), a human osteosarcoma cell line (U2OS), and a healthy cell line (RPE1). Two methods were used to test the antioxidant activity: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). The antibacterial activity was tested in relation to the growth and adhesion of Escherichia coli and Staphylococcus aureus on a polystyrene surface. The GC-MS analysis showed that the major compound in both kumquat essential oils was limonene, which was stable before and after in vitro digestion (>90%). The results showed that the cytotoxic activity of the KEOs in all three cancer cell lines tested was IC50 1–2 mg/mL, and in the healthy cell line (RPE1), the IC50 value was above 4 mg/mL. The antibacterial activity of the KEOs obtained after MAD and Clevenger hydrodistillation was 4 mg/mL against E. coli and 1 mg/mL against S. aureus. The KEOs after MAD and Clevenger hydrodistillation reduced the adhesion of E. coli by more than 1 log, while there was no statistically significant effect on the adhesion of S. aureus to the polystyrene surface. Both KEOs exhibited comparable levels of antioxidant activity using both methods tested, with IC50 values of 855.25 ± 26.02 μg/mL (after MAD) and 929.41 ± 101.57 μg/mL (after Clevenger hydrodistillation) for DPPH activity and 4839.09 ± 91.99 μmol TE/g of EO (after MAD) and 4928.78 ± 275.67 μmol TE/g of EO (after Clevenger hydrodistillation) for ORAC. The results obtained show possible future applications in various fields (e.g., in the food, pharmaceutical, cosmetic, and agricultural industries).

Deciphering the effect of Potentilla fulgens root extract against healthy HUVEC cell line and cancer cell lines (A549 and SKOV-3)

BackgroundPotentilla fulgens, a highly valued indigenous medicinal herb grown in high altitudes of the Himalayan region with anticancer, hypoglycaemic, antibacterial, anti-inflammatory, and antiulcerogenic properties, are used in traditional systems of medicine. This study was aimed to investigate the effect of P. fulgens root extract, as one of the natural alternatives to chemotherapeutic drugs used in cancer treatment, on proliferation, apoptosis, and autophagy of human non-small cell lung cancer cell line (A549), human ovarian cancer cell line (SKOV-3), and healthy human umbilical vein endothelial cell line (HUVEC). MethodsAnti-proliferative effect was assessed by MTT assay. The expression of autophagy and apoptosis-related proteins was evaluated by western blotting. Total oxidant status (TOS) and total antioxidant capacity (TAC) test were determined using standard kit methods. ResultsOur results showed that the extract inhibited proliferation of HUVEC, A549, and SKOV-3 cells in a dose-dependent manner. MTT assay analysis revealed that the extract significantly (P<0.05) induced mortality in HUVEC, A549, and SKOV-3 cells. Western blot results revealed increased expression of NF-κB after the extract treatment but led to the down-regulation in Beclin-1, Bax, extracellular-signal-related kinase 1 and 2, Sequestosome-1, and Cleaved Casp-3 levels. Treatment groups showed an increase in TOS and TAC values in A549 and SKOV-3 cell lines, while HUVEC cell line showed an increase in TAC and a decrease in TOS values, compared to the control group. ConclusionsOur findings indicated that P. fulgens root extract inhibited the proliferation of healthy cells and cancer cells through cell cycle arrest, representing its limited application as therapeutic agent in cancer treatment.

Novel synthetic UV screen compounds inspired in mycosporine-like amino acids (MAAs): Antioxidant capacity, photoprotective properties and toxicity

The combination of environmental stress on the ozone layer, climate change and a greater sun exposure due to outdoor habits has led to an increase in skin cancer cases and other health issues related with UV radiation. Researchers are searching for new alternative UV filters that could protect our skin from the deleterious effects of UV radiation while also presenting low toxicity and biodegradable character (unlike the UV filters currently available in the market). In this work, two compounds inspired in the natural oxo-mycosporine-like amino acids (MAAs) have been synthesized and their antioxidant and photoprotective properties, as well as their in vitro and in vivo toxicity effects were evaluated. Both compounds featured a strong UV-B absorption together with a high antioxidant capacity, close to 50 μmol TE g−1 DW in the ABTS assay. Compound 1 presented an absorption peak at 285–300 nm, whereas compound 2 showed a wider band with a peak around 295–305 nm and two shoulders at 318 and 342 nm. The addition of 5 % of compound 2 to galenic formulas increased the photoprotection, reaching SPF values of 4. Both compounds were stable under UV radiation exposure. Regarding toxicity, the synthetic compounds did not show cytotoxic activity against healthy human cell lines or significant toxicity over zebrafish embryos. Compound 1 showed a complete lack of toxicity over zebrafish, although compound 2 showed slight, not-significant effects on viability, hatching, pericardial stability or body axis formation over 5 mg mL−1. Moreover, compound 1 presented relatively antitumoral activities against HCT-116 cells (selective index:1.49). The relevant antioxidant and photoprotective ability together with the great advantage provided by the reduced toxicity to health cells or zebrafish embryos, make these compounds promising candidates to be exploited as functional ingredients with specific applications in the biotechnological or pharma sector.

Avelumab reduces STAT3 expression with effects on IL-17RA and CD15.

Avelumab is a human antibody that targets the programmed cell death ligand-1 (PD-L1) protein in cancer cells. Novel anticancer therapies for renal cell carcinoma (RCC) consider cluster of differentiation 15 (CD15) and interleukin 17 receptor A (IL-17RA) as potential targets. Notably, the expression of PD-L1, CD15 and IL-17RA is dependent on signal transducer and activator of transcription 3 (STAT3). The aim of the study was to investigate whether targeting PD-L1 with avelumab alters the expression levels of CD15 and IL-17RA, and to assess the STAT3-mediated regulation of CD15 and IL-17RA. We applied immunocytochemistry (ICC) and confocal laser scanning (CLS) microscopy to assess the expression and localization of the immunotherapy targets in 3 renal cancer cell lines and 1 healthy renal cell line. After treatment with 20 ng/mL avelumab, renal cancer cells showed a reduction in STAT3 expression. The expression of CD15 increased in cancer cells that exhibited a high level of IL-17RA, and the membrane signal of CD15 was reduced. In other renal cancer cell lines, the expression of CD15 decreased. Conversely, the level of IL-17RA changed only in healthy renal cells after treatment with avelumab, with no impact on renal cancer cells. Our study suggests that the targeting of PD-L1 with avelumab alters the expression of CD15 and IL-17RA, which play an important prognostic and therapeutic role in novel anticancer therapy.

Methanolic Extract of the Nutritional Plant (Diospyros kaki Thunb.) Exhibits Anticancer Activity by Inducing Mitochondrial Dysfunction in Colorectal Cancer Cells.

Background/Objectives:Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves' extracts contain high amounts of flavonoids and terpenoids, endowed with several beneficial effects. However, its anticancer activity towards colorectal cancer (CRC) has not been investigated in depth. Methods: The effect of a methanolic extract of D. kaki leaves, rich in kaempferol and quercetin derivatives, have been evaluated on an E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS-activating mutation. Results: This extract is effective in reducing tumor cells' viability without affecting the healthy mucosa cell line CCD 841. In fact, Western blot experiments showed its ability to induce apoptosis in cancer cells by increasing oxidative stress and disrupting mitochondrial functionality, as shown by reactive oxygen species measurement and Seahorse analysis. Conclusions: With the aim of increasing healthspan, as well as the substantial societal and macroeconomic costs associated with cancer, our results could pave the way to a role for D. kaki extract in both CRC treatment and prevention.

Anticancer Activity of Green Synthesized Manganese Doped Cerium Oxide Nanoparticles Prepared by Using Acacia Concinna Fruit Extract

AbstractPure CeO2 and Ce1‐xMnxO2, where x = 0, 2, 4 and 6% w/w, were synthesized by sol‐gel method using Acacia Concinna fruit extract as a surfactant and stabilizing agent. The synthesized particles were subjected to various characterization techniques, including XRD, HRTEM, FESEM, FTIR, Raman and UV‐Visible spectroscopy. The XRD pattern of the samples demonstrated single phase of CeO2, with cubic fluorite type structure and crystallite size of 6–7 nm. The morphology of the nanoparticles (NPs) was analyzed by FESEM and HRTEM which illustrated an aggregate of irregular spherical nanoparticles and the average particle size is around 18 nm. Raman spectroscopy validated the phase purity and indicated about the structural defects caused by the dopants. The bandgap energy of CeO2 NPs is calculated to be 3.00 eV from the Tauc plot of UV‐Visible spectroscopy, which gradually decreased to 2.43 eV with increase in manganese doping. Cytotoxicity studies signified the role of Mn‐doped CeO2 NPs as a potential nanotherapeutic agent for cancer treatment. The cell viability assay showed that 200 µg/mL of 6% Mn‐doped CeO2 nanoparticles exhibited remarkable cytotoxic effect by inhibiting 50% of cancer cells both in breast and colon cancer cell lines without affecting the healthy cell lines.

Activated carbon-coated iron oxide magnetic nanocomposite (IONPs@CtAC) loaded with morin hydrate for drug-delivery applications.

Cancer is a major disease that affects millions of people around the world every year. It affects individuals of all ages, races, and backgrounds. Since drugs used to treat cancer cannot distinguish between cancerous and healthy cells, they cause systemic toxicity along with serious side effects. Recently, controlled drug-release systems have been developed to reduce the side effects caused by anticancer drugs used for treatment. Morin is an anticancer drug with a flavonol structure. It has been extensively researched for its antioxidant, anti-inflammatory, antitumoral, and antibacterial properties, especially found in Chinese herbs and fruits, and its multiple positive effects on different diseases. In this study, a nanocomposite with magnetic properties was synthesized by coating biocompatible activated carbon obtained using the fruits of the Celtis tournefortii plant on the surface of iron oxide magnetic nanoparticles. Characterization of the synthesized activated carbon-coated iron oxide magnetic nanocomposite was confirmed by Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray spectrometry, X-ray diffraction, dynamic light scattering, zeta potential, and vibrating sample magnetometry. The cytotoxic effects of the drug-loaded magnetic nanocomposite were examined in HT-29 (colorectal), T98-G (glioblastoma) cancer cell lines, and human umbilical vein endothelial cell (HUVEC) healthy cell line. The morin loading and release behavior of the activated carbon-coated iron oxide magnetic nanocomposite were studied, and the results showed that up to 60% of the adsorbed morin was released within 4h. In summary, activated carbon-coated iron oxide magnetic nanocomposite carriers have shown promising results for the delivery of the morin drug.

Comparison of Essential Oils of Schinus molle L. Leaves Growing in Different Regions of Algeria in Terms of Their Chemical Compositions and Various Biological Activities

ABSTRACTThis preliminary study investigated the chemical composition and biological properties of essential oils derived from Schinus molle L. leaves obtained from three specific regions in Algeria: Algiers (SMA), Djelfa (SMD), and Mascara (SMM). Gas chromatography (GC) and Gas chromatography–Mass Spectrometry (GC–MS) analyses confirmed the presence of 52 compounds (100.0%) in SMA essential oil, 50 compounds (100.0%) in SMD, and 72 compounds (100.0%) in SMM essential oils. The main components of SMA oil were camphene (31.82%), limonene (14.71%), and p‐cymene (9.25%). In SMD and SMM oils, α‐phellandrene (14.25% and 12.70%), limonene (13.02% and 11.90%), and germacrene D (10.62% and 10.15%) were the major components, respectively. The antioxidant characteristics were evaluated using five methods: β‐carotene‐linoleic acid, DPPH, ABTS+, CUPRAC, and Metal chelating assays. The results revealed a moderate to low anti‐oxidant effect, with SMA essential oils exhibiting the highest activity. A moderate inhibitory effect against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α‐glucosidase, α‐amylase, urease, and tyrosinase was observed, indicating anti‐enzymatic activity. Nevertheless, all samples had higher IC50 values for both antioxidant and anti‐enzymatic activities than 200 μg/mL. It was determined that regional differences in the locations where S. molle grows showed both qualitative and quantitative differences in essential oil components. This difference was also detected in the biological activities of the essential oils. The anti‐inflammatory capacities of the three samples were assessed using Human Red Blood Cell (HRBC) membrane stabilisation and egg albumin denaturation techniques. The results showed effective anti‐inflammatory activity in all three samples. The antimicrobial efficacy was evaluated using a range of tests, such as anti‐quorum sensing, violacein inhibition, anti‐swimming, and anti‐swarming assays, demonstrating moderate activity. No toxic effects were observed at the tested dosages when assessing cytotoxicity against a healthy cell line (CCD18‐Co). This thorough examination provides valuable insights into the chemical composition and bioactive properties of essential oils derived from S. molle. These findings indicate the possible use of these essential oils in the food, medicinal, and cosmetic industries.

MELATONIN ENHANCES TEMOZOLOMIDE-INDUCED APOPTOSIS IN GLIOBLASTOMA AND NEUROBLASTOMA CELLS.

The combination of temozolomide (TMZ) and paclitaxel (PTX) is the most commonly used chemotherapy regimen for glioblastoma, but there is no specific treatment for neuroblastoma due to the acquired multidrug resistance. Approximately half of treated glioblastoma patients develop resistance to TMZ and experience serious side effects. Melatonin (MEL), a multifunctional hormone long known for its antitumor effects, has a great advantage in combination cancer therapy thanks to its ability to affect tumors differently than normal cells. This study aims to evaluate the in vitro inhibitory effects of MEL in combination with TMZ on cancer cell viability and to elucidate the underlying mechanisms in the glioblastoma and neuroblastoma cell lines. C6 (Rattus norvegicus) and N1E-115 (Mus musculus) cancer cell lines and C8-D1A (mice) healthy cell lines were used. Cell proliferation was evaluated using the MTT test. IC50 values were determined by probit analysis. Two concentrations of TMZ (IC50 and 1/2 IC50) were used to induce cytotoxicity in the C6 and N1E-115 cell lines, both alone and in combination with PXT and MEL (all at IC50). The viable, dead, and apoptotic cells were determined by image-based cytometry using Annexin V/PI staining. The gene expression related to signaling pathways was assessed by the quantitative reverse transcription polymerase chain reaction (qRT-PCR), and key proteins were identified by the Western blot analysis. MTT assay showed that the combination of TMZ and MEL significantly reduces the viability of both glioblastoma and neuroblastoma cells compared to the vehicle-treated controls. Notably, MEL combined with 1/2 IC50 TMZ showed a significant death rate of cancer cells compared to controls and PTX. According to qRT-PCR data, the TMZ + MEL combination resulted in the upregulation of the genes of antioxidative enzymes (Sod1 and Sod2) and DNA repair genes (Mlh1, Exo1, and Rad18) in both cell lines. Moreover, the levels of Nfkb1 and Pik3cg were significantly reduced following the TMZ + MEL treatment. The combination of MEL with TMZ also enhanced the cell cycle arrest and increased the expression of p53 and pro-apoptotic proteins (Bax and caspase-3), while significantly decreasing the expression of anti-apoptotic protein Bcl-2. Our findings indicate that the combination of MEL with a low dose of TMZ may serve as an upstream inducer of apoptosis. This suggests the potential development of a novel selective therapeutic strategy as an alternative to TMZ for the treatment of both glioblastoma and neuroblastoma.

Synthesis and characterization of activated carbon-supported magnetic nanocomposite (MNPs-OLAC) obtained from okra leaves as a nanocarrier for targeted delivery of morin hydrate.

The method of encapsulating the drug molecule in a carrier, such as a magnetic nanoparticle, is a promising development that has the potential to deliver the medicine to the site where it is intended to be administered. Morin is a pentahydroxyflavone obtained from the leaves, stems, and fruits of various plantsmainly from the Moraceae family exhibiting diverse pharmacological activities such as anti-inflammatory, anti-oxidant, and free radical scavenging and helps treat diseases such as diabetes, myocardial infarction and cancer. In this study, we conducted the synthesis of a nanocomposite with magnetic properties by coating biocompatible activated carbon obtained from okra plant leaves with magnetic nanoparticles. Characterization of the synthesized activated carbon-coated magnetic nanocomposite was confirmed by Fourier transform infrared, scanning electron microscopy, dynamic light scattering, and zeta potential. The cytotoxic effects of the drug-loaded magnetic nanocomposite were examined in HT-29 (Colorectal), MCF-7 (breast), U373 (brain), T98-G (Glioblastoma) cancer cell lines, and human umbilical vein endothelial cells healthy cell line. We studied the loading and release behavior of morin hydrate in the activated carbon-coated magnetic nanocomposite. Activated carbon-coated magnetic nanocomposite carriers can show promising results for the delivery of Morin hydrate drugs to the targeted site.

Synergistic Anticancer Effects by Enhancing the G-Quadruplex Binding of Nickel(II) Salphen Complexes through Coupling with S-Doped Carbon Nanodots.

In recent decades, researchers have focused on developing less toxic and more precise cancer therapies. Carbon nanodots (CDs) are among the most promising technologies due to their high biocompatibility, tunable fluorescence, and ability to facilitate photothermal and photodynamic therapy. This study explores the synthesis and characterization of two CDs conjugated with Salphen metal complexes, namely, CDs-PEG-M1 and CDs-PEG-M2, through Sonogashira coupling. Their interaction with G-quadruplex DNA structures (G4s), motifs largely involved in cancer development, was evaluated using various spectroscopic techniques. The results indicate that CDs-PEG-M1 exhibits greater effectiveness in stabilizing G4 structures compared to the metal complex alone or nonfunctionalized CDs. This enhanced stabilization suggests that CDs-PEG-M1 could reduce the concentration of the metal complex needed for potential antitumor applications, thereby minimizing side effects on nontarget tissues. When tested on breast cancer models (MDA-MB-231 as a triple-negative model and MCF-7 as a HER-2 positive model) and on a healthy cell line (HDFa), the CDs-PEG-M1 conjugate reduced cell viability in a concentration- and time-dependent manner, showing greater potency and selectivity against cancer cells compared to virgin CDs and the free M1 complex. This synergistic anticancer effect, driven by the interaction with G4 structures and reactive oxygen species production, underscores the potential of CDs-PEG-M1 as a targeted nanotheranostic tool.

Synthesis of Carborane–Thiazole Conjugates as Tyrosinase and 11β-Hydroxysteroid Dehydrogenase Inhibitors: Antiproliferative Activity and Molecular Docking Studies

The presented study depicts the synthesis of 11 carborane–thiazole conjugates with anticancer activity, as well as an evaluation of their biological activity as inhibitors of two enzymes: tyrosinase and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The overexpression of tyrosinase results in the intracellular accumulation of melanin and can be observed in melanoma. The overexpression of 11β-HSD1 results in an elevation of glucocorticoid levels and has been associated with the aggravation of metabolic disorders such as type II diabetes mellitus and obesity. Recently, as the comorbidity of melanomas and metabolic disorders is being recognized as an important issue, the search for new therapeutic options has intensified. This study demonstrates that carborane–thiazole derivatives inhibit both enzymes, exerting beneficial effects. The antiproliferative action of all newly synthesized compounds was evaluated using three cancer cell lines, namely A172 (human brain glioblastoma), B16F10 (murine melanoma) and MDA-MB-231 (human breast adenocarcinoma), as well as a healthy control cell line of HUVEC (human umbilical vein endothelial cells). The results show that 9 out of 11 newly synthesized compounds demonstrated similar antiproliferative action against the B16F10 cell line to the reference drug, and three of these compounds surpassed it. To the best of our knowledge, this study is the first to demonstrate dual inhibitory action of carborane–thiazole derivatives against both tyrosinase and 11β-HSD1. Therefore, it represents the first step towards the simultaneous treatment of melanoma and comorbid diseases such as type II diabetes mellitus.

Exploring the therapeutic potential of microwave-assisted biosynthesized silver nanoparticles using Erica manipuliflora Salisb.: A comprehensive study on anticancer and antibacterial potentials

Silver nanoparticles (AgNPs) continue to attract interest due to their potential applications in biomedicine, especially in relation to their antibacterial and anticancer properties. In this respect, it is important to develop biosynthesis techniques that are environmentally friendly and include new sources. This is the first report on microwave-assisted green synthesis of silver nanoparticles using Erica manipuliflora Salisb. (E.m AgNPs). In this study, the anti-cancer and antibacterial activity of E.m AgNPs and E. manipuliflora extracts were evaluated. Characterization of E.m AgNPs were performed using UV–Vis spectroscopy FT-IR, XRD, SEM and TEM analyses. The UV–Vis absorption spectrum showed the characteristic peak of E.m AgNPs at λmax = 425 nm. The SEM and TEM results indicated that the nanoparticles were spherical and ranged in size from 2.45 to 9.95 nm. The antibacterial results, it was determined that E.m AgNPs (50 mg mL−1) (8.4–21.1 mm ZOI) caused more effective inhibition on both gram positive (Bacillus subtilis, Staphylococcus aureus, Enterococcus faecalis) and gram negative (Escherichia coli) bacteria compared to all plant extracts (50 mg mL−1) (8.13–17.16 mm ZOI). Among the cancer (MCF-7 and HT-29) and healthy (HaCaT and HEK-293) cell lines, E.m AgNPs exhibited the highest cytotoxicity against MCF-7 cells (IC50: 87.22 μg mL−1). The hexane extract was the most effective inhibitory extract on cell proliferation of all cell lines and showed the highest cell inhibition in MCF-7 cells (IC50: 43.06 μg mL−1). The results revealed that both E.m AgNPs and E. manipuliflora extracts showed promising antibacterial activity against pathogenic bacterial strains and had potential anticancer activity.

Synthesis of novel skipped diene-3-halocoumarin conjugates as potent anticancer and antibacterial biocompatible agents

Cancer and bacterial infections are persistent nightmares for human health, which are now aggravated by the development of new types of cancer and pathogenic bacteria, as well as their resistance to prescribed drugs. To be part of a hopeful awakening, this work aimed to synthesize four novel skipped diene-3-halocoumarin conjugates coded SDC1-SDC4 and explore their biosafe functions as anticancer and antibacterial alternatives. In the first step of their synthesis, mequinol reacts with ethyl-2-haloacetoacetate through a H2SO4-catalyzed Pechmann reaction, yielding 3-halo-6-methoxy-4-methylcoumarins. The in situ-generated Vilsmeier-Haack reagent formylated these trifunctionalized coumarins to create their 7-carbaldehyde congeners. Finally, the target conjugates were prepared by condensing the latter compounds with 2,4-pentadione through the modified Claisen-Schmidt reaction. The molecular structures involving their stereochemistry were established for SDC1-SDC4 by analyzing their spectra released from FTIR, 1H NMR, 13C NMR, and HRMS. On the other hand, the anticancer and cytotoxicity of these conjugates were investigated against eight cancer and three healthy cell lines, respectively, using an MTT-probing technique. Four pathogenic and three commensal aerobes were the microbes utilized to evaluate the antibacterial and microbiota compatibility, respectively, employing a broth microdilution methodology. The results indicated that the conjugate with the highest anticancer attribute and lowest cytotoxicity was SDC1, while SDC2 demonstrated the greatest antibacterial attribute with minimal microbiota toxicity. These findings projected the influence of a 3-position substitute of the coumarin backbone on the biological activities under research. From these, it is concluded that the chemical structures of SDC1 and SDC2 may represent potent anticancer cytocompatible and antibacterial microbiota-compatible scaffolds, respectively.

Hyperthermia and biological investigation of a novel magnetic nanobiocomposite based on acacia gum-silk fibroin hydrogel embedded with poly vinyl alcohol

The design and synthesis of biocompatible nanostructures for biomedical applications are considered vital challenges. Herein, a nanobiocomposite based on acacia hydrogel, natural silk fibroin protein, and synthetic protein fibers of polyvinyl alcohol was fabricated and magnetized with iron oxide nanoparticles (Fe3O4 MNPs). The structural properties of the hybrid nanobiocomposite were investigated by essential analyses such as Fourier Transform Infrared Spectrometer (FTIR), Field emission scanning electron microscopy (FE-SEM), and X-ray powder diffraction)XRD(analyses, Thermogravimetric and Differential thermogravimetric analysis (TGA-DTG), Vibrating-sample magnetometry (VSM), and Energy Dispersive X-Ray Analysis (EDX). The biological activities and functional properties of the prepared magnetic nanobiocomposite were studied. Results proved that this nanobiocomposite is non-toxic to the healthy HEK293T cell line. In addition, the synthesized nanobiocomposite showed an approximately 22 % reduction in cell viability of BT549 cells after 72 h. All results confirmed the anti-cancer properties of nanobiocomposite against breast cancer cell lines. Therefore, the prepared nanobiocomposite is an excellent material that can use for in-vivo application. Finally, the hyperthermia application was evaluated for this nanobiocomposite. The SAR was measured 93.08 (W/g) at 100 kHz.

Innovative Fluorescent Polymers in Niosomal Carriers: A Novel Approach to Enhancing Cancer Therapy and Imaging.

Cancer is anticipated to become the pioneer reason of disease-related deaths worldwide in the next two decades, underscoring the urgent need for personalized and adaptive treatment strategies. These strategies are crucial due to the high variability in drug efficacy and the tendency of cancer cells to develop resistance. This study investigates the potential of theranostic nanotechnology using three innovative fluorescent polymers (FP-1, FP-2, and FP-3) encapsulated in niosomal carriers, combining therapy (chemotherapy and radiotherapy) with fluorescence imaging. These cargoes are assessed for their cytotoxic effects across three cancer cell lines (A549, MCF-7, and HOb), with further analysis to determine their capacity to augment the effects of radiotherapy using a Linear Accelerator (LINAC) at specific doses. Fluorescence microscopy is utilized to verify their uptake and localization in cancerous versus healthy cell lines. The results confirmed that these niosomal cargoes not only improved the antiproliferative effects of radiotherapy but also demonstrate the practical application of fluorescent polymers in in vitro imaging. This dual function underscores the importance of dose optimization to maximize therapeutic benefits while minimizing adverse effects, thereby enhancing the overall efficacy of cancer treatments.

Novel hydrazide-hydrazone containing 1,2,4-triazole as potent inhibitors of antiapoptotic protein Bcl-xL: Synthesis, biological evaluation, and docking studies.

This study describes the synthesis and characterization of a series of novel hydrazide-hydrazone derivatives containing a 1,2,4-triazole ring. The compounds were characterized using various spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antiproliferative activity of the synthesized compounds was evaluated against a panel of human cancer cell lines (HCT-116, HepG-2, KLN205, LTPA, U138, and SW620) and healthy cell lines (HSkMC and iPSCs). Among the compounds tested, compounds 4, 5p, 5r, and 5s showed the highest effectiveness in inhibiting the growth of cancer cells with Bcl-xL inhibitory concentration (IC50) values. These compounds further demonstrated selective cytotoxicity against the Bcl-xL-dependent lymphoma cell line (DBs). Molecular docking studies were also performed to investigate the potential binding interactions of compounds 4, 5p, 5r, and 5s with the active site of Bcl-xL (PDB ID: 7LH7, 1.4 Å). Mechanistic studies revealed that compounds 4, 5r, and 5s induced apoptosis predominantly through the intrinsic mitochondrial pathway, while compound 5p exhibited a distinct cell cycle arrest profile, impacting both the S and G2/M phases. Western blot analysis suggested that these compounds may downregulate cyclin expression, thereby blocking its association with Bcl-xL. Overall, these results demonstrate the potential of these novel hydrazide-hydrazone derivatives as anticancer agents with activity comparable or superior to doxorubicin and 5-fluorouracil.

Determination of Cytotoxic Activity of Aronia melanocarpa (Michx.) Elliot Fruit Extracts on Breast Cancer (MCF-7) and Cervical Cancer (HeLa) Cell Lines

Aronia (chokeberry) fruits are consumed as fresh fruit due to their high antioxidant activity, and are also preferred among the public in the production of natural medicines. Aronia melanocarpa (Michx.) Elliot, a species of the Rosaceae family, contains many phytochemical compounds such as flavonoids, phenolic compounds, lignans, terpenes, tocopherols, phospholipids, organic acids and high amounts of anthocyanins. In this study, it was aimed to determine the in vitro anticarcinogenic activities of A. melanocarpa (Michx.) Elliot fruit extracts prepared with 6 different solvents. In the study, the cytotoxic effects of the fruits were investigated using breast cancer cell line (MCF-7) and cervical cancer cell line (HeLa), and their effects on healthy cells were investigated using human endothelial cells (HUVEC) and mouse fibroblast cells (L929) by the MTT method. As a result of the study; It was determined that the highest cytotoxicity on the breast cancer (MCF-7) cell line was observed in the ethanol extract (IC50=111.44 µg/mL) and the lowest cytotoxicity was observed in the hexane extract (IC50=661.80 µg/mL). It was determined that the highest cytotoxicity on the cervical cancer (HeLa) cell line was observed in the ethanol extract (IC50=95.14 µg/mL) and the lowest cytotoxicity was observed in the ethyl acetate extract (IC50=319.51 µg/mL). According to these values; It was determined that all extracts of Aronia fruit had cytotoxic effects on MCF-7 and HeLa cell lines, selectivity index values were higher in HeLa cells, and they did not have cytotoxic effects on HUVEC and L929 healthy cell lines (IC50=411.25-663.27 µg/mL). Thus, it has been determined that the fruits of the Aronia melanocarpa species are promising in the development of new natural resources, new drugs and therapeutic agents in cancer treatment, thanks to their anticancer activities and low cytotoxicity. It is recommended that further research be conducted on the mechanisms of anticancer activity in the future

DRUG PRECURSOR TARGETING THE BOMBESIN RECEPTOR FOR PEPTIDE-RECEPTOR RADIONUCLIDE THERAPY

Cancer is a leading cause of death worldwide. A promising modality for cancer treatment is peptide receptor radionuclide therapy. Therapeutic radionuclide is delivered using peptide-based vectors, which can bind to specific receptors on the cancer cell surface. Bombesin receptors are one of the receptors peculiar to many types of cancer, which can be targeted by peptide vectors. Peptides have a number of advantages, but they also have one serious drawback: low stability in the internal environment. To solve the problem, it is possible to the include a therapeutic peptide in the structure of a highly stable knottin peptide. Objective. The aim of the study is to examine the stability of BBN/C1-C2 structure, created on the basis of U5-scytotoxinSth1a knottin and bombesin tropic to bombesin receptor, and the ability of this structure to bind to target receptors on the cancer cell surface. Materials and Methods. BBN/C1-C2 peptide was obtained by solid-phase peptide synthesis. Then, is underwent chromatography purification under analytical chromatography and mass spectrometry control. Stability was studied by analytical chromatography. Competitive inhibition analysis was carried out using a fluorescently labeled GRP peptide with excess BBN/C1-C2 and fluorescently labeled BBN/C1-C2 with GRP bombesin receptor inhibitor. Cancer cell line PC-3 expressing bombesin receptors and normal cell line CHO-K1 not expressing bombesin receptors were used in the work. Results. The conducted studies have shown that hybrid BBN/C1-C2 peptide based on bombesin peptide inserted into the U5-scytotoxinSth1a knottin framework between the first and second cysteine residues has a greater stability compared to the commercial radiopharmaceutical PSMA-617. BBN/C1-C2 peptide is specific to bombesin receptor: it binds to PC-3 cancer cell line with a target bombesin receptor on its surface, and does not bind to the healthy CHO-K1 cell line, without a target receptor. BBN/C1-C2 peptide shows high affinity for the bombesin receptor, since GRP prevents its binding to the PC-3 cell line.

Therapeutic potential of 18-β-glycyrrhetinic acid-loaded poly (lactic-co-glycolic acid) nanoparticles on cigarette smoke-induced in-vitro model of COPD

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions. This study investigates the possible potential of poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles encapsulating the plant-based bioactive compound 18-β-glycyrrhetinic acid (18βGA) as a strategy to intervene in cigarette smoke extract (CSE)-induced oxidative stress, inflammation, and senescence, in vitro. We prepared 18βGA-PLGA nanoparticles, and assessed their effects on cell viability, reactive oxygen species (ROS) production, anti-senescence properties (expression of senescence-associated β galactosidase and p21 mRNA), and expression of pro-inflammatory genes (CXCL-1, IL-6, TNF-α) and inflammation-related proteins (IL-8, IL-15, RANTES, MIF). The highest non-toxic concentration of 18βGA-PLGA nanoparticles to healthy human broncho epithelial cell line BCiNS1.1 was identified as 5 µM. These nanoparticles effectively mitigated cigarette smoke-induced inflammation, reduced ROS production, protected against cellular aging, and counteracted the effects of CSE on the expression of the inflammation-related genes and proteins. This study underscores the potential of 18βGA encapsulated in PLGA nanoparticles as a promising therapeutic approach to alleviate cigarette smoke-induced oxidative stress, inflammation, and senescence. Further research is needed to explore the translational potential of these findings in clinical and in vivo settings.