Normal Human Fibroblast Cell Line Research Articles

Cytotoxic constituents from the fruit of Solanum aculeastrum

A new triterpene, aculeastrumone A (1), a new triterpene saponin aculeastrumoside A (2), and eleven known compounds (3–13) were isolated from MeOH/Water (80/20) extract of the fruits of Solanum aculeastrum (Solanaceae). Their structures were established by detailed 1D and 2D NMR spectroscopic studies and mass spectrometry. The isolated compounds were evaluated against three human cancer cells ((MCF-7 (breast cancer), NCI-H460 (lung cancer), and Hela (cervical cancer)) and normal human fibroblast (BJ) cell lines. Among them, saponins 2–5, 7–8, and Carpesterol 10 possess significant cytotoxic activity with IC50 ≤ 10 µM against the three cancer cell lines.

Cytotoxic constituents of Cymbidium tracyanum L.Castle

Three phenanthrene derivatives, cymbisamoquinone (1), calanquinone B (6), and 3,7-dihydroxy-2,4,6- trimethoxyphenanthrene (2), and two bibenzyls, Tristin (3) and gigantic (4), together with the lignan (+)-pinoresinol (5), were isolated from the whole plants of Cymbidium tracyanum L.Castle (Orchidaceae). Their structures were determined through spectroscopic analysis as well as a comparison of the spectral data with literature values. The phytochemical constituents of this plant have been reported for the first time. All isolated compounds were evaluated for in vitro cytotoxic activity against human colon (Caco-2) and breast (MCF-7) cancer cell lines, doxorubicin-resistant (MCF-7/DOX) and mitoxantrone-resistant (MCF-7/MX) MCF-7 sublines, together with normal human fibroblast (NIH/3T3) cell line. Among the isolated compounds, 1 exhibited the strongest and relatively selective activity on MCF-7/DOX cells. The results obtained from the molecular docking study suggested that the cytotoxicity of 1 on MCF-7/DOX cells was possibly due to the induction of apoptosis via suppression of the cell survival systems mediated by the mitogen-activated protein kinases and protein kinase B/glycogen synthase kinase-3β/nuclear factor erythroid 2-related factor 2 signalling pathways.

Nutritional Profiling, Antioxidant Potential and Collagen Building Properties of Lacto-Fermented, Microencapsulated Guava Juice Powder

Fermented products consist beneficial probiotics, which makes these products render improved nutritional properties and health effects. There is a need for research to explore and establish the use of commonly existing fruits in fermented forms for application in skincare and as anti aging solutions.This study has been conducted to establish collagen building and antioxidant potential of fermented guava fruit juice powder.The human dermal fibroblast cells were used to determine the collagen building potential while chemical enzymatic assays were used to evaluate antioxidant properties of fermented guava juice powder (FGJP) . The antioxidant activity evaluated by the ability to scavenge DPPH radicals showed very high anti-oxidative capacity (IC50 = 0.015 mg/ml) comparable to ascorbic acid (IC50 = 0.018 mg/ml). This antioxidant potential can be attributed to the presence of various phytonutrients, primarily flavonoid (quercetin equivalent) at a concentration of 38 mcg/mg of the powder. The Collagen building potential was evaluated on the normal human fibroblast cell line . The levels of Collagen IV involved in skin cell migration, regeneration, and wound healing were estimated. FGJP imparted proliferation ability in NHDF cells at the concentrations of 0.025, 0.05, and 0.1mg/ml,which is 31% collagen synthesis against untreated cell control. This explains that fermented guava juice powder has a collagen building potential along with antioxidant properties. Such product would be helpful in providing a plant based anti aging solutions especially for vegan consumers.The optimized fermented guava juice powder has a shelf life of 45 days when stored at refrigerated conditions with a potential for combating oxidative stress and supporting in alleviating the aging symptoms like fine-line, wrinkle through collagen building.

Imidazole derivatives as novel and potent antifungal agents: Synthesis, biological evaluation, molecular docking study, molecular dynamic simulation and ADME prediction

Fungal infections have become a serious threat to human health due to their high incidence and mortality. In this study, a new set of imidazole derivatives (7a-f) were synthesized and their chemical structures were characterized using spectroscopic techniques including IR, 1H-NMR, 13C-NMR and Mass. In the following, the antifungal activities of these derivatives were evaluated against several yeasts, aspergillus and dermatophyte species using the CLSI method. In addition, to check the safety of the synthesized compounds, the in vitro cytotoxicity activity of these compounds was investigated towards normal human fibroblasts cell line (MRC-5) using MTT assay. The obtained biological results indicated that these compounds acted as the most potential antifungal agents. In particular, compounds 7c, 7d and 7f exhibited excellent activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, Candida dubliniensis, Candida parapsilosis, and Cryptococcus neoformans species with MIC50 values in the range of 0.5-16 µg/ml. The cytotoxicity results showed that these compounds have low toxicity against normal human fibroblasts cell line (MRC-5). Additionally, molecular modelling studies and molecular dynamic simulation were carried out to predict the binding energy and possible interaction mode of these compounds in the binding site of lanosterol 14α-demethylase (CYP51) as a conventional target for azole derivatives. In silico ADME study was also performed to investigate the physicochemical features of the synthesized imidazole derivatives. According to the results, these compounds can be considered as promising antifungal candidates for further development.

Exploring NiFe2O4 nanoparticles: Electrochemical analysis and evaluation of cytotoxic effects on normal human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cell lines

Nanobiotechnology facilitates the development of novel materials with potential applications in human health, the environment, and a variety of industries. We used X-ray diffraction (XRD) to characterize NiFe2O4 nanoparticles (NPs), confirming a cubic crystal structure with crystallite sizes of 19 nm and 21 nm. Synthesized NPs spherical shape morphology was confirmed by field emission-scanning electron microscopy (FE-SEM) and an average diameter (prepared NPs) of 20 nm and 23 nm was revealed by Transmission electron microscopy (TEM). The chemical state was determined using X-ray photoelectron spectroscopy (XPS). A vibrating sample magnetometer (VSM) was used to measure the magnetic characteristics. The electrochemical characteristics of prepared electrodes could be useful for supercapacitor applications. Changing the surfactants, reaction temperature, and heating duration considerably enhanced electrochemical performance, according to our findings. At 700 °C, specific capacitance (Cs) attained an outstanding value of 67.2 F/g. The prepared NPs cytotoxicity was performed on normal human dermal fibroblast (HDF) and mouse melanoma (B16-F10) cell lines. The current findings show that these NPs are non-toxic at concentrations ranging from 0 to 1000 µg/mL. These findings point to prospective biomedical uses for NiFe2O4 NPs.

Effect of Glycolipoprotein Biosurfactant from Enterococcus faecium on the viability of Breast cancer cell lines.

Objective : This study , was research for cytotoxicity of bio-surfactant created by Enterococcus faecium isolated from feces of Iraqi healthy breast-fed infants with  age < 6 months.
 Methods :  Cold acetone precipitation was used to the extraction of extracellular Glycolipoprotein biosurfactant and partially purify it. Biosurfactant was then evaluated against two the cell lines, a Breast cancer MCF-7 cell line and a human normal fibroblast cell line NHF), specifically for cell survival and proliferation.  
 Results :  At all concentrations  with varying percentage, The viability of the MCF-7 cancer cell line was shown to be reduced with the addition of biosurfactant.; maximum inhibition percentage was 74.2% at a 100 µg/ml concentration, which is lesser than 45.5% cytotoxicity Of NHF healthy fibroblasts cell line.
 Conclusions : The findings of this study are highly encouraging in terms of the potential of Glycolipoprotein biosurfactants to treat cancer and encourage additional research with different cell lines.

Application of microalgal-ZnO-NPs for reusing polyester/cotton blended fabric wastes after modification by cellulases enzymes

Polyester/cotton (PET/C) blended fabric wastes are produced daily in huge amounts, which constitutes an economic loss and an environmental threat if it is not reused appropriately. Modern textile waste recycling technologies put much effort into developing fabric materials with unique properties, such as bioactivity or new optical goods based on modern technologies, especially nano-biotechnology. In this study, zinc oxide nanoparticles (ZnO-NPs) were biosynthesized using the aqueous extract of Dunaliella sp. and immobilized on PET/C waste fabrics after enzymatically activated with cellulases. The produced Dunaliella-ZnO-NPs (10–20 nm with a spherical shape) were characterized by High-resolution transmission electron microscopy (HRTEM), Fourier-transform infrared spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Scanning electron microscopy-energy dispersive X-ray analyzer (SEM-EDAX), and some functional groups, such as CH, CO, NH, and CN (due to the presence of carboxyl, proteins and hydroxyl groups), were detected, revealing the biosynthesis of ZnO-NPs. The analysis showed that the resulting ZnO-NPS had potent antimicrobial effects, Ultraviolet (UV) protection capabilities, and no cytotoxic effects on the normal human fibroblast cell line (BJ1). On the other hand, enzymatic treatments of PET/C fabric waste with cellulases enhanced the immobilization of biosynthetic nanoparticles on their surface. Modified PET/C fabrics loaded with Dunaliella-ZnO-NPs showed antibacterial and UV protection capabilities making them an eco-friendly and cost-effective candidate for numerous applications. These applications can include the manufacture of active packaging devices, wastewater treatment units, and many other environmental applications.Graphical abstract

Porous Poly(2-hydroxyethyl methacrylate) Hydrogel Scaffolds for Tissue Engineering: Influence of Crosslinking Systems and Silk Sericin Concentration on Scaffold Properties.

Tailored porous structures of poly(2-hydroxyethyl methacrylate) (PHEMA) and silk sericin (SS) were used to create porous hydrogel scaffolds using two distinct crosslinking systems. These structures were designed to closely mimic the porous nature of the native extracellular matrix. Conventional free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) was performed in the presence of different concentrations of SS (1.25, 2.50, 5.00% w/v) with two crosslinking systems. A chemical crosslinking system with N'N-methylene bisacrylamide (MBAAm) and a physical crosslinking system with dimethylurea (DMU) were used: C-PHEMA/SS (crosslinked using MBAAm) and C-PHEMA/pC-SS (crosslinked using MBAAm and DMU). The focus of this study was on investigating the impact of these crosslinking methods on various properties of the scaffolds, including pore size, pore characteristics, polymerization time, morphology, molecular interaction, in vitro degradation, thermal properties, and in vitro cytotoxicity. The various crosslinked networks were found to appreciably influence the properties of the scaffolds, especially the pore sizes, in which smaller sizes and higher numbers of pores with high regularity were seen in C-PHEMA/1.25 pC-SS (17 ± 2 μm) than in C-PHEMA/1.25 SS (34 ± 3 μm). Semi-interpenetrating networks were created by crosslinking PHEMA-MBAAm-PHEMA while incorporating free protein molecules of SS within the networks. The additional crosslinking step involving DMU occurred through hydrogen bonding of the -C=O and -N-H groups with the SS, resulting in the simultaneous incorporation of DMU and SS within the PHEMA networks. As a consequence of this process, the scaffold C-PHEMA/pC-SS exhibited smaller pore sizes compared to scaffolds without DMU crosslinking. Moreover, the incorporation of higher loadings of SS led to even smaller pore sizes. Additionally, the gelation time of C-PHEMA/pC-SS was delayed due to the presence of DMU in the crosslinking system. Both porous hydrogel scaffolds, C-PHEMA/pC-SS and PHEMA, were found to be non-cytotoxic to the normal human skin dermal fibroblast cell line (NHDF cells). This promising result indicates that these hydrogel scaffolds have potential for use in tissue engineering applications.

Cocrystallization of methyltestosterone with salicylic acid and 2,2′-disulfanediyldibenzoic acid - Effect on solubility of methyltestosterone and growth of leishmania parasite (amastigotes and promastigotes)

Methyltestosterone is a class II anabolic androgenic steroidal drug, structurally resembled to natural testosterone, produced by body. Two cocrystals of methyltestosterone with thiosalicylic acid and salicylic acid were successfully furnished by using solid state grinding method with the aim to study changes in biological activities and solubility. During cocrystallization the coformer thiosalicylic acid dimerize into 2, 2′-disulfanediyldibenzoic acid and furnished co-crystal I. Characterization of cocrystals 1 and II was carried out on the basis of single-crystal X-ray diffraction technique, IR spectroscopy, DSC/TGA analysis. The solubility of prepared cocrystals I and II were found to be significantly improved in different dissolution media i.e. phosphate buffer (pH 6.8, 7.4), 0.1 N HCl and distill water. Methyltestosterone and both cocrystals were found to be non-cytotoxic while tested against BJ human normal fibroblast cell line. Non-cytotoxic cocrystals I and II were further evaluated for anti-leishmanial activity (amastigotes and promastigotes). Both cocrystal I (IC50 = 11.9 µM) and II (IC50 = 27.2 µM) shows potent anti-leishmanial activity against L. major promastigote (extracellular / in blood parasite stage) and amastigote (intracellular / inside macrophage cell) stage in comparison to the standard drugs miltefosine (IC50 = 25.5 ± 0.42 µM) and methyltestosterone (IC50 = 37.42±0.57 µM). Infected macrophage cellular assay together with AFM analysis are carried out to study the effect of synthesized cocrystals on growth of amastigotes stage of L. major. The promising result demonstrates the effect of cocrystallization on solubility and anti-leishmanial potential of anabolic androgenic steroidal drug methyltestosterone for the first time.

Single-cell analysis of human dermal fibroblasts isolated from a single male donor over 35 years.

The aim of this study is to examine the effects of ageing on dermal fibroblast heterogeneity based on samples obtained from the same donor. We used a dermal fibroblast lineage (named ASF-4 cell lines) isolated from the inner side of the upper arm of a healthy male donor over a 35-year period, beginning at 36 years of age. Because clonal analysis of ASF-4 cell lines demonstrated a donor age-dependent loss of proliferative capacity and acquisition of senescent traits at the single-cell level, cultured cells frozen at passage 10 at ages 36 and 72 years were subjected to single-cell RNA sequencing. Transcriptome analysis revealed an increase in senescent fibroblasts and downregulation of genes associated with extracellular matrix remodelling with ageing. In addition, two putative differentiation pathways, with one endpoint consisting of senescent fibroblasts and the other without, were speculated using a pseudo-time analysis. Knockdown of the characteristic gene of the non-senescent fibroblast cluster endpoint, EFEMP2, accelerated cellular senescence. This was also confirmed in two other normal human dermal fibroblast cell lines. The detection of a common cellular senescence-related gene from single-donor analysis is notable. This study provides new insights into the behaviour of dermal fibroblasts during skin ageing.

Optimization and characterization of antileukemic l-asparaginase produced by Fusarium solani endophyte

l-asparaginase is an antileukemic enzyme that hydrolyzes l-asparagine into l-aspartic acid and ammonia, causing cell starvation and apoptosis in susceptible leukemic cell populations. Currently, l-asparaginase obtained from bacterial sources is constrained by several issues, including lesser productivity, stability, selectivity, and higher toxicity. The goal of this study is to provide fungal l-asparaginase with in-vitro effectiveness towards different human carcinomas. l-asparaginase from endophytic Fusarium solani (Gene Bank accession number MW209717) isolated from the roots of the medicinal plant Hedera helix L. was characterized and optimized experimentally for maximum l-asparaginase production in addition to evaluating its subsequent cytotoxicity towards acute monocytic leukemia and human skin fibroblast cell lines. The enzyme production was maximized using potato dextrose media (15.44 IU/ml/hr) at the 5th and 6th days of fermentation with incubation temperature 30 °C, 3% asparagine, 150–180 rpm agitation rate and a 250 ml flask. Enzyme characterization studies revealed that the enzyme maintained its thermal stability with temperatures up to 60 °C. However, its optimal activity was achieved at 35 °C. On measuring the enzymatic activity at various temperatures and different pH, maximum enzyme activity was recorded at 40 °C and pH 8 using 0.1 M asparagine concentration. Results also revealed promising cytotoxic activity against acute monocytic leukemia with IC50 = 3.66 µg/ml and low cytotoxicity against tested normal human skin fibroblast cell line which suggested that it might have selective toxicity, and consequently it could be used as a less toxic alternative to the current formulations.

Synthesis and characterization of CeO2/MgFe2O4 nanocomposites for electrochemical study and their cytotoxicity in normal human dermal fibroblast (HDF) and human breast cancer (MDA-MB-231) cell lines

In this study, we investigated the effect of size variation in CeO2/MgFe2O4 nanocomposites (NCs) on their electrochemical (EC) performance and cytotoxicity. To adjust particle size, the NCs were synthesized using an auto-combustion process and subsequently at various (500, 600, 700, and 800 °C) calcined temperatures (CTs). The crystallite size was determined using X-ray diffraction (XRD), and the NCs spherical shape was validated using field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The chemical components on the surface of the NCs were discovered using an X-ray photoelectron spectroscopy (XPS). The different size distributions of CeO2/MgFe2O4 NCs as electroactive materials in supercapacitors and measured their EC performance in 1 M KOH using cyclic voltammetry (CV), galvanostatic charge/discharge (GCD) and electrochemical impedance spectroscopy (EIS). The CeO2/MgFe2O4 NCs revealed a good cell survival rate in cytotoxicity studies, showing their biocompatibility. The NCs were found to be harmless to HDF and MDA-MB-231 cancer cell lines, highlighting their potential for biological applications in the future.

Stereo- and Regio-selective benzo- and Benzohalo-conduritols: Anti-diabetes &anti-tumor activity investigation, kinetic and molecular docking studies

In this study, benzoconduritols, benzohalogenoconduritol, and benzodihalogenoconduritols with conduritol-A and –C structures from oxo-norbornene derivative endo-10 b, exo-11 b cleavaged by Lewis acids (BBr3, BCl3, BF3· OEt2) and Ac2O/H2SO4 were defined. These compounds (10a, 24, 25, 26, 27, 28, 29, 34, and 35) have been evaluated for their potential to inhibit the α-glucosidase enzyme against acarbose-positive control. Among the compounds, halogen-substituted compounds 24, 25, 27, and 34 showed potent inhibition of the α-glucosidase enzyme compared with acarbose, while other compounds showed moderate inhibition. The kinetic studies of the most active compounds 24, 25, 27, and 34 were evaluated, then determined that they were mixed, non-competitive, and competitive type inhibitors. In addition, the in vitro cytotoxicity activities of these compounds were tested against human breast (BT-20), melanoma (SK-MEL128), prostate (DU-145), liver (SNU-398), lung (A549) cancer, and normal human fibroblast (HFC) cell lines. Among these compounds, the dichloro-substituted compound 25 showed the highest cytotoxic effect in the range of CC50 = 11.5–31.6 μg/mL against SNU-398, DU-145, SK-MEL128, A549, and HFC cell lines. The experimentally determined α-glucosidase and anticancer activity were studied by docking studies to demonstrate the binding orientation and interaction of the synthesized compound with amino acid residues present in the active site of human Maltase–Glucoamylase, topoisomerase II alpha, and Anaplastic Lymphoma Kinase enzymes.

Comparative study of antimicrobial potential and DNA/BSA binding affinity of silver(I) and gold(III) coordination compounds with 1,6-naphthyridine

In the present study, synthesis of silver(I) and gold(III) coordination compounds with 1,6-naphthyridine (1,6-naph), {[Ag(1,6-naph)(H2O)](BF4)}n (1) and [AuCl3(1,6-naph)] (2), was reported. The methods used for the structural characterization of a new compound 1 included IR, NMR (1H and 13C) and UV–Vis spectroscopy, cyclic voltammetry and single-crystal X-ray diffraction analysis. The crystallographic results showed that compound 1 represents silver(I) coordination polymer, in which 1,6-naph ligand acts as a bidentate bridging ligand connecting two Ag(I) ions via its N1 and N6 nitrogen atoms, while the third coordination site of the metal ion is occupied by the water oxygen atom, resulted in a T-shape geometry. Compounds 1 and 2 were evaluated in vitro for antimicrobial activity against five bacterial and two Candida species, while their cytotoxicity was tested on the normal human lung fibroblast cell line (MRC-5). Compound 1 has manifested a remarkable antifungal activity on both tested Candida strains (C. albicans and C. parapsilosis) with minimal inhibitory concentrations (MICs) of 1.43 and 11.38 µM (0.49 and 3.9 µg/mL), respectively, while no significant antimicrobial activity was observed for 2. Moreover, silver(I) coordination polymer 1 inhibits the hyphae formation of C. albicans at subinhibitory concentration. The binding affinity of both compounds 1 and 2 with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied by fluorescence spectroscopy, indicating their ability to interact with these biomolecules, with compound 2 being more reactive.

Anticandidal Cu(I) complexes with neocuproine and 1-(4-methoxyphenyl)piperazine based diphenylaminomethylphosphine: Is Cu-diimine moiety a pharmacophore?

The studies on metal complexes as potential antifungals are of growing interest because they may be the answer to increasingly effective defense mechanisms. Herein we present two new copper(I) iodide or thiocyanide complexes with 2,9-dimethyl-1,10-phenanthroline (dmp) and diphenylphosphine derivative of 1-(4-methoxyphenyl)piperazine (4MP): [CuI(dmp)4MP] (1-4MP) and [CuNCS(dmp)4MP] (2-4MP) - their synthesis, as well as structural and spectroscopic characteristics. Interestingly, while 4MP and its oxide derivative (4MOP) show a very low or no activity against all tested Candida albicans strains (MIC50 ≥ 200 μM against CAF2–1 - laboratory control strain, DSY1050 - mutant without transporters Cdr1, Cdr2, Mdr1; isogenic for CAF2–1, and fluconazole resistant clinical isolates), for 1-4MP and 2-4MP MIC50 values were 0.4 μM, independently on the complex and strain tested. Determination of the viability of NHDF-Ad (Normal Adult Human Dermal Fibroblasts) cell line treated with 1-4MP and 2-4MP showed that for both complexes there was only a 20% reduction in the concentration range ¼ to 2 × MIC50 and the 70% at 4 × MIC50. Subsequently, the MLCT based luminescence of the complexes in aqueous media allowed to record the confocal micrographs of 1-4MP in the cells. The results show that it is situated most likely in the vacuoles (C. albicans) or lysosomes (NHDF-Ad).

Fabrication and characterization of nanodelivery platform based on chitosan to improve the anticancer outcome of sorafenib in hepatocellular carcinoma

Chitosan nanoparticles (CS NPs) showed promising results in drug, vaccine and gene delivery for the treatment of various diseases. The considerable attention towards CS was owning to its outstanding biological properties, however, the main challenge in the application of CS NPs was faced during their size-controlled synthesis. Herein, ionic gelation reaction between CS and sodium tripolyphosphate (TPP), a widely used and safe CS cross-linker for biomedical application, was exploited. The development of nanodelivery platform, namely Sorafenib-loaded chitosan nanoparticles (SF–CS NPs), was constructed in order to improve SF drug delivery to human Hepatocellular Carcinoma (HepG2) cell lines. The NPs were artificially fabricated using an ionic gelation technique. A number of CS NPs that had been loaded with an SF were prepared using different concentrations of sodium tripolyphosphate (TPP). These concentrations were 2.5, 5, 10, and 20 mg/mL, and they are abbreviated as SF–CS NPs 2.5, SF–CS NPs 5.0, SF–CS NPs 10, and SF–CS NPs 20 respectively. DLS, FTIR, XRD, HRTEM, TGA, and FESEM with EDX and TEM were used for the physiochemical characterisation of SF–CS NPs. Both DLS and HRTEM techniques demonstrated that smaller particles were produced when the TPP content was raised. In a PBS solution with a pH of 4.5, the SF exhibited efficient release from the nanoparticles, demonstrating that the delivery mechanism is effective for tumour cells. The cytotoxicity investigation showed that their anticancer effect against HepG2 cell lines was significantly superior than that of free SF. In addition, the nanodrug demonstrated an absence of any detectable toxicity to normal adult human dermal fibroblast (HDFa) cell lines. This is a step towards developing a more effective anticancer medication delivery system with sustained-release characteristics, which will ultimately improve the way cancer is managed.

Assessing the cytotoxicity of phenolic and terpene fractions extracted from Iraqi Prunus arabica on AMJ13 and SK-GT-4 human cancer cell lines

Background: Breast and esophageal cancer are the most aggressive and prominent causes of death worldwide. In addition, these cancers showed resistance to current chemotherapy regimens with limited success rates and fatal outcomes. Recently many studies reported the significant cytotoxic effects of phenolic and terpene fractions extracted from various Prunus species against different cancer cell lines. As a result, it has a good chance to be tested as a complement or replacement for standard chemotherapies. Methods: The study aimed to evaluate the cytotoxicity of phenolic and terpene fractions extracted from Iraqi Prunus arabica on breast (AMJ13) and esophageal (SK-GT-4) cancer cell lines by using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Analysis using the Chou-Talalay method was performed to assess the synergistic effect between the extracted fractions and chemotherapeutic agent (docetaxel). Moreover, high-performance liquid chromatography (HPLC) analysis was conducted for the quantitative determination of different bioactive molecules of both phenolic and terpene fractions in the extract. Results: According to the findings, the treatment modalities significantly decreased cancer cell viability of AMJ13 and SK-GT-4 and had insignificant cytotoxicity on the normal cells (normal human fibroblast cell line) (all less than 50% cytotoxicity). Analysis with Chou-Talalay showed a strong synergism with docetaxel on both cancer cell lines (higher cytotoxicity even in low concentrations) and failed to induce cytotoxicity on the normal cells. Important flavonoid glycosides and terpenoids were detected by HPLC, in particularly, ferulic acid, catechin, chlorogenic acid, β-sitosterol, and campesterol. Conclusions: In conclusion, the extracted fractions selectively inhibited the proliferation of both cancer cell lines and showed minimal cytotoxicity on normal cells. These fractions could be naturally derived drugs for treating breast and esophageal cancers.

Novel phenoxyacetylthiosemicarbazide derivatives as novel ligands in cancer diseases

Numerous epidemiological studies report an increased risk of developing prostate cancer in patients with melanoma and an increased risk of developing melanoma in patients with prostate cancer. Based on our previous studies demonstrating the high anticancer activity of thiosemicarbazides with a phenoxy moiety, we designed nineteen phenoxyacetylthiosemicarbazide derivatives and four of them acting as potential dual-ligands for both cancers. All of the compounds were characterized by their melting points and 1H, 13C NMR and IR spectra. For selected compounds, X-ray investigations were carried out to confirm the synthesis pathway, identify the tautomeric form and intra- and intermolecular interaction in the crystalline state. The conformational preferences and electronic structure of molecules were investigated by theoretical calculation method. Lipophilicity of compounds (log kw) was determined using isocratic reversed phase/high pressure liquid chromatography RP-18. For the obtained compounds, in vitro tests were carried out on four melanoma cell lines (A375, G-361, SK-MEL2, SK-MEL28), four prostate cancer cell lines (PC-3, DU-145, LNCaP, VcaP) and a normal human fibroblast cell line (BJ). The most active compounds turned out to be F6. Cell cycle analysis, apoptosis detection, CellROX staining and mitochondrial membrane potential analysis were performed for the most sensitive cancer cells treated with most active compounds. DSC analysis was additionally performed for selected compounds to determine their purity, compatibility, and thermal stability. The process of prooxidation was proposed as a potential mechanism of anticancer activity.

Targeting SOX18 Transcription Factor Activity by Small-Molecule Inhibitor Sm4 in Non-Small Lung Cancer Cell Lines

The transcription factor SOX18 has been shown to play a crucial role in lung cancer progression and metastasis. In this study, we investigated the effect of Sm4, a SOX18 inhibitor, on cell cycle regulation in non-small cell lung cancer (NSCLC) cell lines LXF-289 and SK-MES-1, as well as normal human lung fibroblast cell line IMR-90. Our results demonstrated that Sm4 treatment induced cytotoxic effects on all three cell lines, with a greater effect observed in NSCLC adenocarcinoma cells. Sm4 treatment led to S-phase cell accumulation and upregulation of p21, a key regulator of the S-to-G2/M phase transition. While no significant changes in SOX7 or SOX17 protein expression were observed, Sm4 treatment resulted in a significant upregulation of SOX17 gene expression. Furthermore, our findings suggest a complex interplay between SOX18 and p21 in the context of lung cancer, with a positive correlation observed between SOX18 expression and p21 nuclear presence in clinical tissue samples obtained from lung cancer patients. These results suggest that Sm4 has the potential to disrupt the cell cycle and target cancer cell growth by modulating SOX18 activity and p21 expression. Further investigation is necessary to fully understand the relationship between SOX18 and p21 in lung cancer and to explore the therapeutic potential of SOX18 inhibition in lung cancer.

Biological effect of natural chitosan nanoparticles with transformed roots extract of Leonotis nepetifolia (L.) R.Br. in an in vitro model

Nanotechnology is a rapidly growing field of science that has a considerable impact on many branches of medicine. Nanoparticles are developing at a rapid pace due to their effect which is achieved by combining them with drugs as well as their increased importance in the drug delivery system. Synthesis of chitosan nanoparticles by ionic gelation is becoming increasingly important due to its low cost and environmentally friendly approach. This preliminary study was the first one to investigate the cytotoxic effect of chitosan nanoparticles with combination of Leonotis nepetifolia (L.) R.Br. transformed root extract against cervical cancer (HeLa), breast cancer (MCF-7), glioma cancer (MO59J) cell lines and normal human fibroblast (Hs68) cell line. Besides, a preliminary analysis of apoptosis induced by caspase 3/7, microscopic observations of morphology changes and apoptosis-related genes expression in cancer cells have been showed. According to MTT results, the synthesized chitosan nanoparticles in combination with Leonotis nepetifolia normal and transformed root extracts showed a stronger cytotoxic effect on all tested cancer lines (HeLa, MCF-7 and MO59J), compared with the nanoparticles and the extracts alone, with IC50 = 0.608, 0.306, 0.112 mg/mL, respectively. In contrast, no cytotoxic effect was shown against the human fibroblast (Hs68) line in the tested concentration range. Preliminary induction of apoptosis showed changes in cell morphology, genes expression and caspase 3/7 activation after treatment with chitosan nanoparticles in combination with normal and transformed from Leonotis nepetifolia root extracts. These discoveries have positive implications for further studies on development of nanoparticles in anti-cancer therapy. The key objective of this work is to test the anti-cancer potential of L. nepetifolia transformed root extract obtained by agrotransformation in combination with natural chitosan nanoparticles as a component capable of enhancing the effect of the extract against various in vitro models.