Normal Fibroblast Cells Research Articles

Biocompatibility, Antimicrobial and Wound Healing Activities of Lavandula dentata Leaves Extract

Background: The human skin is a natural barrier that protects against external stress, but its physiological structure can be compromised when it gets damaged. In the field of medical science, wounds are a significant issue that requires immediate attention. Lavandula species are used in the food, perfume and cosmetics industries due to their antimicrobial, anti-inflammatory and wound-healing properties. Methods: The present study was done to assess the biocompatibility, antimicrobial and wound-healing potential of L. dentata leave methanolic extract (LE) that is cultivated in the Taif region of Saudi Arabia. The biocompatibility of LE was analyzed against the normal human skin fibroblast (HSF) cell line using SRB assay. A quarter of LE IC50 was used for wound healing assay. Finally, Escherichia Coli, Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes were used to determine LE antibacterial potential through the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) measurement. Result: LE appears safe on HSF cell line with IC50 = 97 mg/mL. LE decreased wound width, wound area and the mean cell migratory rate of wound border cells during scratch closure, while increased the wound closure% in a time-dependent manner compared to negative control. LE shows antimicrobial potential against all four strains at MIC and MBC greater than 3.0 mg/mL, except for Streptococcus pyogenes MIC= 3.0 mg/mL. In conclusion, LE offers therapeutic benefits against wound healing with an antimicrobial effect, however, higher concentrations of LE should be used to assess its effect.

Plakevulin A induces apoptosis and suppresses IL-6-induced STAT3 activation in HL60 cells

(+)-Plakevulin A (1), an oxylipin isolated from an Okinawan sponge Plakortis sp. inhibits enzymatic inhibition of DNA polymerases (pols) α and δ and exhibits cytotoxicity against murine leukemia (L1210) and human cervix carcinoma (KB) cell lines. However, the half-maximal inhibitory concentration (IC50) value for cytotoxicity significantly differed from those observed for the enzymatic inhibition of pols α and β, indicating the presence of target protein(s) other than pols. This study demonstrated cytotoxicity against human promyelocytic leukemia (HL60), human cervix epithelioid carcinoma (HeLa), mouse calvaria-derived pre-osteoblast (MC3T3-E1), and human normal lung fibroblast (MRC-5) cell lines. This compound had selectivity to cancer cells over normal ones. Among these cell lines, HL60 exhibited the highest sensitivity to (+)-plakevulin A. (+)-Plakevulin A induced DNA fragmentation and caspase-3 activation in HL60 cells, indicating its role in apoptosis induction. Additionally, hydroxysteroid 17-β dehydrogenase 4 (HSD17B4) was isolated from the HL60 lysate as one of its binding proteins through pull-down experiments using its biotinylated derivative and neutravidin-coated beads. Moreover, (+)-plakevulin A suppressed the activation of interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3). Because the knockdown or inhibition of STAT3 induces apoptosis and HSD17B4 regulates STAT3 activation, (+)-plakevulin A may induce apoptosis in HL60 cell lines by suppressing STAT3 activation, potentially by binding to HSD17B4. The present findings provide valuable information for the mechanism of its action.

Irinotecan-loaded magnetite-silica core-shell systems for colorectal cancer treatment

Colorectal cancer represents a worldwide spread type of cancer and it is regarded as one of the leading death causes, along with lung, breast, and prostate cancers. Since conventional surgical resection and chemotherapy proved limited efficiency, the use of alternative drug delivery systems that ensure the controlled release of cytostatic agents possess immense potential for treatment. In this regard, the present study aimed to develop and evaluate the efficiency of a series of irinotecan-loaded magnetite-silica core–shell systems. The magnetite particles were obtained through a solvothermal treatment, while the silica shell was obtained through the Stöber method directly onto the surface of magnetite particles. Subsequently, the core–shell systems were physico-chemically and morpho-structurally evaluated trough X-ray diffraction (XRD) and (high-resolution) transmission electron microscopy ((HR-)TEM) equipped with a High Annular Angular Dark Field Detector (HAADF) for elemental mapping. After the irinotecan loading, the drug delivery systems were evaluated through Fourier-transform infrared spectroscopy (FT-IR), thermogravimetry and differential scanning calorimetry (TG-DSC), and UV–Vis spectrophotometry. Additionally, the Brunauer–Emmett-Teller (BET) method was employed for determining the surface area and pore volume of the systems. The biological functionality of the core-shells was investigated through the MTT assay performed on both normal and cancer cells. The results of the study confirmed the formation of highly crystalline magnetite particles comprising the core and mesoporous silica layers of sizes varying between 2 and 7 nm as the shell. Additionally, the drug loading and release was dependent on the type of the silica synthesis procedure, since the lack of hexadecyltrimethylammonium bromide (CTAB) resulted in higher drug loading but lower cumulative release. Moreover, the nanostructured systems demonstrated a targeted efficiency towards HT-29 colorectal adenocarcinoma cells, as in the case of normal L929 fibroblast cells, the cell viability was higher than for the pristine drug. In this manner, this study provides the means and procedures for developing drug delivery systems with applicability in the treatment of cancer.

Assessing the antioxidant properties of Naringin and Rutin and investigating their oxidative DNA damage effects in breast cancer

This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness.

Chemical constituents of Lasiodiplodia theobromae BPPCA 144, an endophytic fungus, isolated from Aglaia argentea Blume

Endophytic fungi from Aglaia argentea have indicated the prospective to produce secondary metabolites with unique activities, making them promising candidates for anticancer drug development. This study aimed to investigate the secondary metabolites produced by Lasiodiplodia theobromae BPPCA144, isolated from A. argentea. L. theobromae BPPCA144 was found to produce seven compounds: 2-phenylethanol (1), tyrosol (2), 2-(4-hydroxyphenyl)acetic acid (3), (-)-mellein (4), colletopeptide B (5), botryorhodine A (6), and (4R*,6R*)-4-hydroxy-6-n-propyl-1-oxacyclohexan-2-one (7). These compounds were isolated using vacuum liquid and radial chromatography, and their chemical structures were elucidated through 1D-NMR, 2D-NMR analysis, compared with previously reported spectral data. Notably, compounds (5) and (7) were identified as original from L. theobromae. Among the tested compounds, compound (2) exhibited the strongest activity against MCF-7 breast cancer cells. However, compounds (1, 3, 5 and 7) showed insufficient activity against CV-1 cell lines (normal kidney fibroblast cells).

Cytotoxic Effect of Phoenix dactylifera (Iraqi Date) Leaves and Fruits Extracts against Breast Cancers Cell Lines.

Now a day's cancerous diseases are the most prevalent life threatening that spreading because of the lifestyle. Its due to uncontrolled growth of cell which can be cured if diagnosed in early stage. Treatment of cancer depends on the various internal and external factors causing cancer. The main objective of this study is using herbal based medicine to manage breast cancer, the second most common type of cancer in the world. In this study, the anticancer effect of two Iraqi date palm part extracts (leaves and fruits) against panel of breast cancer cell lines (AMJ13و MCF7, MDA-MB-231, CAL51) in vitro to evaluate their possible antitumor effect and their safety on normal cell line (MEF). The Phoenix dactylifera (dray Zahdi) fresh leave extract showed highly cytotoxic effects in all breast cancer cell lines. The leaves extract was showed concentration dependent cytotoxicity effects after 72 h exposure time. Leave extracts was effective against AMJ13 cell line. The effective concentrations in both cancer cells ranged from 2500-20000 μg/ ml with inhibition percentage against AMJ13 was (66.7, 70.6, 53, and 54%). While the effect against MCF7, MDA-MB, and CAL51 cell lines were less with significant effect only at two concentrations (10000- 20000 μg/ ml) causing 64.3, and 64.3% growth inhibition respectively in MCF7, and 40, and 50% respectively in MDA-MB, and 44.0, and 52.0% respectively in CAL51. The dray date fruit extract has no significant cytotoxicity against all the cancer cells. Both extracts have no effect against normal fibroblast cells. In conclusion, Phoenix dactylifera fresh leave extract shows promising anticancer properties while the fruit extract has no direct anticancer effect.

Exploring MIL-68(Al) nanocarrier for melatonin delivery: probing pro-oxidant effects in cancer cells and achieving sustained drug release

This study explored the synthesis of MIL-68(Al), characterized its properties, and investigated its ability to encapsulate and release melatonin (MEL) in response to changes in pH, intending to develop a more effective drug delivery system. Analyses were directed to characterize the designed nanocarriers before and after drug loading. The drug loading efficiency (DLE) and drug loading content (DLC) of MIL-68(Al) were 78.8% and 44.0%, respectively. The extended drug release period of MEL@MIL-68(Al) was observed to exhibit a faster release under acidic conditions compared to neutral conditions. The cell treatment with free MEL, MIL-68(Al), and MEL@MIL-68(Al) was completed, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed at lung cancer A549 cells and normal fibroblastic MRC-5 cells for the cytotoxicity study. MEL@MIL-68(Al) was more cytotoxic than MIL-68(Al) in A549 cells. Analyzing reactive oxygen species (ROS) levels via fluorescent microscopic analysis showed ROS overproduction in cells treated with MEL@MIL-68(Al) in comparison to other interventions. Additionally, MEL@MIL-68(Al) modulated the protein expression levels of Nrf-2, Keap-1, and HO-1 in cells. Therefore, MEL@MIL-68(Al) exerts its potent anticancer effects via ROS overproduction and downregulation of the Nrf2/Keap-1 pathway. Therefore, this system can be a promising nanoplatform for the successful delivery of MEL and potentiating its anticancer effects.

Evaluating the Biocompatibility of Maxillofacial Silicone Enhanced by Hexagonal Boron Nitride Particles

This study aims to evaluate the biocompatibility of a novel filler material intended to improve the longevity of polymer systems used in prosthetics in respect of cytotoxicity and skin irritation. RTV50F silicone elastomer incorporated with various percentages of hexagonal boron nitride (H-BN) (0.1, 0.3, 0.5, 0.7, and 1 wt%) have been tested. Silicone without H-BN was utilized as the control for comparison. The in vitro cytotoxicity test includes specimens (n=18) with 10 mm in diameter and 2 mm in thickness applied directly to the normal human fibroblast cell line (NHF) and incubated for 72 hours, then 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cell viability. The skin irritation test was conducted in vivo, in which specimens (n=12) with 25 mm × 25 mm dimensions were applied on the back of 5 different rabbits for 4 hours, then the skin response was evaluated after 24, 48, and 72 hours. The acquired in vitro data were statically analyzed using one-way ANOVA and post-hoc Tukey’s tests with GraphPad Prism 8, where P-value < 0.05 was considered statistically significant. The H-BN powder and silicone specimens were studied via field emission scanning electron microscopy (FE-SEM). The results revealed a negligible effect of maxillofacial silicone on cell viability after 72 hours of incubation, only one group (1wt%) showed a significant difference compared to the control group but the toxicity percentage didn’t exceed 30% of cell viability and there was no skin irritation during the in vivo test.

Evaluation of Bioactivity of Ethanol and Water Extracts and Determination of Nutrient Concentrations of Laurel (Laurus nobilis) Plants Grown in İzmir Province

This study was conducted to determination of ethanol and water extracts obtained from the leaves of Laurus nobilis (Laurel) plant of the general content by GC-MS analysis, antimicrobial activities of these extracts on some microorganisms, total antioxidant levels (TAS), total oxidant levels (TOS), oxidative stress index (OSI) values, anti-carcinogenic effects on various cell lines and macro and micronutrient concentrations of Laurel (Laurus nobilis) plants cultivated for decorative purposes in parks and gardens of Izmir province of Turkey. TAS, TOS, and OSI values were determined with the aid of Rel Assay Diagnostics kits. In antimicrobial activity analysis, the minimum inhibition concentration (MIC) of the plant extracts against microorganisms was determined by microdilution broth method. Staphylococcus aureus (ATCC 29213), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), Bacillus cereus (ATCC11778), Candida albicans (ATCC 10231) and Candida tropicalis (DSM11953) microorganisms were used in this analysis. Furthermore, cytotoxic activities of plant extracts were determined by XTT method in normal rat fibroblast cell line, HUVEC, and 2 different human cancer cell lines. At the end of the study, it was found that ethanol and water extracts of the Laurel plants had no antimicrobial activity, low oxidative stress index and good antioxidant activity, and moderate cytotoxic activity on experimented cell lines. Nitrogen (N), Phosphorus (P), Potassium (P), Calcium (Ca), Magnesium (Mg), Iron (Fe), Zinc (Zn), Manganese (Mn) and Copper (Cu) concentrations of plant extracts were respectively identified as 1.68% N, 0.72% P, 1.12% K, 2.40% Ca, 0.45% Mg, 147.4 mg/kg Fe, 13.6 mg/kg Zn, 326.3 mg/kg Mn and 27.8 mg/kg Cu.

Formulation and characterization of ionically crosslinked gellan gum hydrogels using trilysine at low temperatures for antibody delivery

Research of the nontraditional polysaccharide gellan gum (GG) is a growing space for the development of novel drug delivery systems due to its tunable physic-mechanical properties, biocompatibility, and stability in a wide range of environments. Unfortunately, high temperature crosslinking is often required, representing a limiting factor for the incorporation of thermosensitive therapeutic agents. Here, we demonstrated that GG can be crosslinked at a low temperature (38 °C) using a simple fabrication process that utilizes trilysine as an alternative to traditional mono- or divalent ion crosslinkers. While elevated temperature mixing is still required to form a clear GG solution, crosslinking of 0.5 – 1 % GG (w/v) in the presence of trilysine (0.03 % - 0.05 % w/v) was achieved at 38 °C resulting in hydrogels with suitable working formulations to facilitate syringe loading. Low injection forces (< 20 N), and biocompatibility was evaluated with normal human dermal fibroblast (cell viability > 90 %). Frequency sweep showed a transition from purely liquid-like behavior to gel-like behavior with increased trilysine concentration. A temperature dependent behavior was lost with higher trilysine concentrations, indicating stable hydrogel formation. NMR results suggest that trilysine participates in gelation via both ionic interactions between the primary amines of trilysine and the carboxylate residues of glucuronic acid and hydrogen bonding. Released studies showed that GG hydrogels can entrap and provide sustained release of IgG in relation to the crosslinker, and antibody concentration used, with a burst release within the first 24 h (∼80 % cumulative released) followed by a sustained released for up to 5 days. Overall, findings demonstrate a promising nontoxic injectable hydrogel that requires lower crosslinking temperatures, is simple to manufacture and serves as a carrier of thermosensitive therapeutic agents.

Design, synthesis, antineoplastic activity of new pyrazolo[3,4-d]pyrimidine derivatives as dual CDK2/GSK3β kinase inhibitors; molecular docking study, and ADME prediction

In the current study, novel pyrazolo[3,4-d]pyrimidine derivatives 5a–h were designed and synthesized as targeted anti-cancer agents through dual CDK2/GSK-3β inhibition. The designed compounds demonstrated moderate to potent activity on the evaluated cancer cell lines (MCF-7 and T-47D). Compounds 5c and 5 g showed the most promising cytotoxic activity against the tested cell lines surpassing that of the used reference standard; staurosporine. On the other hand, both compounds showed good safety and tolerability on normal fibroblast cell line (MCR5). The final compounds 5c and 5 g showed a promising dual CDK2/GSK-3β inhibitory activity with IC50 of 0.244 and 0.128 μM, respectively, against CDK2, and IC50 of 0.317 and 0.160 μM, respectively, against GSK-3β. Investigating the effect of compounds 5c and 5 g on CDK2 and GSK-3β downstream cascades showed that they reduced the relative cellular content of phosphorylated RB1 and β-catenin compared to that in the untreated MCF-7 cells. Moreover, compounds 5c and 5 g showed a reasonable selective inhibition against the target kinases CDK2/GSK-3β in comparison to a set of seven off-target kinases. Furthermore, the most potent compound 5 g caused cell cycle arrest at the S phase in MCF-7 cells preventing the cells’ progression to G2/M phase inducing cell apoptosis. Molecular docking studies showed that the final pyrazolo[3,4-d]pyrimidine derivatives have analogous binding modes in the target kinases interacting with the hinge region key amino acids. Molecular dynamics simulations confirmed the predicted binding mode by molecular docking. Moreover, in silico predictions indicated their favorable physicochemical and pharmacokinetic properties in addition to their promising cytotoxic activity.

Antiviral and cytotoxic activities and chemical profiles of two species of Abies nordmanniana from Türkiye.

Abies is an important genus of the family Pinaceae, with about 50 species found in the highlands of Asia, Europe, North Africa, and North and Central America. The principal aim of the present work was to investigate the chemical content and biological potential of the resin and cone from Abies nordmanniana subsp. bornmulleriana and Abies nordmanniana subsp. equi-trojani, respectively. The flavonoid and phenolic contents of the resin and cones were evaluated using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Additionally, the essential oil and fatty acid compositions were analyzed using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detector (GC-FID), respectively. Cytotoxicity of the extracts and essential oils were screened against certain cancer cell lines, namely, human prostate adenocarcinoma cell line (PC3), human lung adenocarcinoma cell line (A549), human pancreatic cancer cell line (PANC-1), human hepatocellular carcinoma cell line (HepG2), human breast cancer cell line (MDA-MB231), and normal human lung fibroblast cell line (CCD-34-LU), with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay. According to the MTT results, hexane extracts of both cone (CH) and resin (RH), ethanol-water (CEW), dichloromethane (CD), and acetone (CA) extracts of the cone mostly inflict cytotoxicity in HepG2 cell line. Antiviral activities of Abies nordmanniana subsp. extracts at doses of 5 μg/g and 10 μg/g were also evaluated in ovo for their virucidal activity against avian coronavirus. Abies nordmanniana subsp. extracts exhibited concentration-dependent antiviral activity on specific pathogen-free embryonated chicken eggs. Significantly, cone acetone extract (CA), cone ethanol extract (CE), and cone dichloromethane extract (CD) of Abies nordmanniana subsp. exhibited strong inhibition of the virus at a concentration of 10 μg/g. The most potent virucidal activity was observed with ethanol-water extract of conifer form (CEW). According to these results, it was proved that Abies nordmanniana species could be a potential, sustainable, and renewable drug source, especially considering the impressive antiviral and significant cytotoxic activity potentials.

Next generation antimitotic β-carboline derivatives modulate microtubule dynamics and downregulate NF-κB, ERK 1/2 and phospho HSP 27

AimExploring the efficacy of β-carboline-based molecular inhibitors in targeting microtubules for the development of novel anticancer therapeutics. Materials and methodsWe synthesized a series of 1-Aryl-N-substituted-β-carboline-3-carboxamide compounds and evaluated their cytotoxicity against human lung carcinoma (A549) cells using the MTT assay. Normal lung fibroblast cells (WI-38) were used to assess compound selectivity. The mechanism of action of MJ-211 was elucidated through Western blot analysis of key pro-apoptotic and cell cycle regulatory proteins. Additionally, the inhibitory effect of MJ-211 on multicellular 3D spheroid growth of A549 cells was evaluated. Key findingsLead compound MJ-211 exhibited remarkable cytotoxicity against A549 cells with an IC50 of 4.075 μM at 24 h treatment and IC50 of 1.7 nM after 72 h of treatment, while demonstrating selectivity towards normal WI-38 cells. MJ-211 activated pro-apoptotic factors Bim and p53, and suppressed Cyclin B1, Phospho HSP 27, BubR1, Mad 2, ERK1/2, and NF-κB, indicating its potent antimitotic and pro-apoptotic effects. MJ-211 significantly suppressed the migration of cells and inhibited the growth of A549 cell-derived multicellular 3D spheroids, highlighting its efficacy in a more physiologically relevant model. SignificanceCytotoxic effect of MJ-211 against cancer cells, selectivity towards normal cells, and ability to modulate key regulatory proteins involved in apoptosis and cell cycle progression underscore its potential as a promising template for further anticancer lead optimization. Moreover, the inhibitory effect of MJ-211 on multicellular spheroid growth suggests its efficacy in combating tumor heterogeneity and resistance mechanisms, thereby offering a promising avenue for future anticancer drug development.

Chemo-immunotherapy by nanoliposomal epacadostat and docetaxel combination to IDO1 inhibition and tumor microenvironment suppression

The over-activation of tryptophan (Trp) metabolism to kynurenine (Kyn) catalyzed by Indoleamine 2,3-dioxygenase-1 (IDO1) enzyme, is one of the main metabolic pathways involved in tumor microenvironment (TME) immune escape and cancer treatment failure. The most efficient of IDO1 inhibitors is Epacadostat (EPA). Since monotherapy with single-agent IDO1 inhibitor regimen has led to an insufficient anti-tumor activity, we examined the efficacy of simultaneous treatment by Liposomal epacadostat (Lip-EPA) as a potent IDO inhibitor, in combination with docetaxel (DTX) as a complement immunogenic cell death (ICD) agent against B16F10 model. First, the in vitro combination index (CI) of epacadostat (EPA) and DTX was investigated by using the unified theory. Then, the in vivo efficacy of the combination therapy was assessed. Results indicated the synergestic cytotoxic effect of the combination on B16F10 compared to normal fibroblast cells (NIH). The immune profiling demonstrated a significant increase in the percentage of infiltrated T lymphocytes and IFN-γ release, a significant decrease in the percentage of regulatory T cells (Treg) population and the subsequent low levels of IL-10 generation in mice treated with Lip-EPA + DTX. Further, a significant tumor growth delay (TGD = 69.15 %) and an increased life span (ILS > 47.83 %) was observed with the combination strategy. Histopathology analysis revealed a remarkable increase in the Trp concentration following combination treatment, while Kyn levels significantly decreased. Results showed that the nano-liposomal form of IDO1 inhibitor in combination with chemotherapy could significantly improve the imunity response and dominate the tumor immuno-suppressive micro-environment, which merits further investigations.

Genetic insights and therapeutic potential for colorectal cancer: mutation analysis of KRASgene and efficacy of Oleuropein-conjugated iron oxide nanoparticles.

This study aimed to address the challenges of treating advanced stages of colon cancer (CRC) by exploring potential therapeutic options. The research focused on the genetic aspects of CRC, specifically the mutation rate of the KRAS gene, along with other genes like TTN, APC, MUC16, and TP53, using the TCGA dataset. Additionally, the study investigated the efficacy of Oleuropein, a polyphenolic compound found in olives, in combating CRC by using iron oxide nanoparticles coated with glucose and conjugated with Oleuropein. The study characterized the physicochemical properties of the nanoparticles, and the cytotoxic effects of the nanoparticles were evaluated on CRC and normal fibroblast cell lines, demonstrating significantly higher cytotoxicity against CRC cells compared to normal cells. Furthermore, the study analyzed gene expression changes using the GSE124627 dataset to understand the influence of KRAS alterations. It identified numerous upregulated and downregulated genes in KRAS-overexpressing samples, suggesting their involvement in critical cancer-related pathways. These findings suggest that KRAS-influenced genes could serve as potential therapeutic targets for CRC treatment. The study also examined the expression levels of identified genes in CRC samples compared to normal samples. Among the upregulated genes, 22 showed significant increases in cancer samples, while 14 downregulated genes exhibited decreased expression in both KRAS-influenced and cancer samples. Cox regression analysis identified specific upregulated genes, including ANKZF1, SNAI1, PPFIA4, SIX4, and NOTUM, associated with poor prognosis. Kaplan-Meier analysis further confirmed the correlation between increased expression of these genes and higher patient mortality rates. In conclusion, this study provided valuable insights into the genetic aspects of CRC and potential therapeutic strategies. The use of Oleuropein-conjugated iron oxide nanoparticles showed promising cytotoxic effects on colon cancer cells. These findings contribute to advancing our understanding of CRC and offer potential targets for further investigation and the development of novel therapeutic approaches.

Enhancement in Anticancer Activity of Chitosan Tailored Imidazole-2-Thiosemicarbazones against MCF-7 Cancer Cell Line by Coordination with Copper(II) Ions

The coordination behavior of new batch synthesized chitosan imidazole-2-thiosemicarbazones tailored from both the low molecular weight commercial chitosan and high molecular weight crab shell chitosan was confirmed by Fourier Transform Infrared (FT-IR) and magnetic susceptibility measurements. Chlorine content in the complexes was estimated by potentiometric titration technique. The study showed the tridentate NNS tridentate coordination with copper (II) ion in a square planar orientation with the remaining valence satisfied by coordination with chloride ion. The MTT assay studies showed an enhancement in the anticancer activity of these chitosan thiosemicarbazone ligands upon their coordination with copper (II) ions against the human breast cancer (MCF-7) cell line in vitro. The minimal cytotoxicity of both the ligands and complexes against the normal mouse embryonic fibroblast (NIH3T3) cells revealed the selective attraction of these biomaterial chitosan derivatives towards the cancer cells with non-toxicity to healthy cells. There was only a marginal effect of molecular weight (Mw) and degree of deacetylation (DDA) of chitosan upon the anticancer activity of these chitosan derivatives.

Synthesis and characterization of sulfonamide appended rigid phenyl-based and non-rigid 1,4-benzodioxan-based ring systems and their Pt(II) complexes towards potential therapeutic targets

Two novel non-rigid; 1,4-benzodioxan (bzd) based and rigid; 4-methylbiphenyl (4-Mebip) based di-(2-picolyl)amine derived sulfonamide ligands, and their cis-dichloroplatinum(II) complexes have been synthesized. The ligands; L1: N(SO2)(bzd)dpa and L2: N(SO2)(4-Mebip)dpa were synthesized via N-sulfonylation of di-(2-picolyl)amine in good yield. Their platinum(II) complexes; C1: [PtCl2(N(SO2)(bzd)dpa)], C2: [PtCl2(N(SO2)(4-Mebip)dpa)]·CH3CN were synthesized and characterized by 1H NMR, FTIR, UV–Vis and fluorescence spectroscopies. Structural studies revealed that the L1 and L2 ligands coordinate Pt(II) in a bidentate mode in C1 and C2 complexes, forming an eight-membered chelate ring. Interestingly, L1 possesses two conformations because the dioxan ring exists with a 95:5 occupancy ratio. The L2 ligand crystal undergoes a phase transition to triclinic form with twinning at 90 K whereas, at 150 K, the ligand exists in a monoclinic system; the populations of the two orientations for one pyridine substituent are approximately 78:22. The 1H NMR spectra of both Pt complexes obtained in DMSO‑d6 revealed two doublets (exo-CH2 and endo-CH2) for the magnetically inequivalent methylene protons, in contrast to their uncoordinated ligands, which show a singlet peak for the methylene protons. The NCI-H292 (non-small cell lung cancer cells) and MRC-5 (human normal lung fibroblast cells) were used to examine the in vitro cytotoxic activity of all synthesized compounds. All tested compounds demonstrated notable cytotoxicity against NCI-H292 cells, with the most pronounced cytotoxic effect being displayed by [PtCl2(N(SO2)(4-Mebip)dpa)]·CH3CN (C2). Docking studies strengthen in vivo antiproliferation activity where specific interactions with AKT1, BAX, STK-11, and BCL-2 were explored. Further predictions revealed that the compounds have inhibitory effects on COX-2 and PDE10A proteins.

Barleria lupulina leaf extract-assisted biosynthesis of cobalt ferrite nanoparticles: Characterization and anticancer activity against MCF-7 cells

This study reports the synthesis of Cobalt ferrite (CoFe2O4) nanoparticles (NPs) by a green synthesis method using the leaf extract of Barleria Lupulina. The X-ray diffraction (XRD) analysis confirms the formation of a single-phase cubic (Fd3m) structure and from the Scherrer formula the average crystallite size (30.07 nm) calculated matches with that obtained from W-H plot(34.66 nm). A bandgap of 2.02 eV was observed from the UV–Vis-DRS analysis. Fourier transform infrared spectroscopy (FTIR) was used to confirm the characteristic functional groups present in the spinel ferrite. The investigation using scanning electron microscopy (SEM) shows aggregates of nanoparticles and EDX analysis gives the chemical composition of the green synthesized ferrite sample. The distribution of particle-sizes and colloidal-stability were estimated by DLS and zeta-potential measurements. The M−H plot confirmed the ferromagnetic nature of the prepared nanoparticles. Beyond the realm of material science, we ventured into the realm of biological activity. Our synthesized cobalt ferrite nanoparticles were assessed for their toxicity on human breast cancer cell lines (MCF-7) as well as normal L929 fibroblast cell lines by MTT assay. The results show potent anti-cancer activity of the ferrite sample (LC50 value 77.92 µg/ml) while sparing normal cells from excessive toxicity (LC50 value 252.34 µg/ml). The results of cell viability, changes in cell morphology, and cell cycle analysis revealed that cobalt ferrite nanoparticles triggered apoptosis, and hindered cell adhesion and migration of MCF-7 cells, potentially through elevated reactive oxygen species generation. This dual action, where the nanoparticles combat cancer effectively while minimizing harm to healthy cells, holds significant promise in the field of oncology.

Synthesis, structural investigations, in vitro cytotoxicity, apoptotic activity, cell cycle analysis, and molecular modeling studies of nano‐sized Zn(II) Schiff base complex

A new novel tetradentate ligand, [(1E,1′E)‐N,N′‐(1,2‐phenylene)bis(1‐(5‐(2‐fluorophenyl)furan‐2‐yl)methanimine) (PFPFMI), and its nano‐sized [Zn(PFPFMI)Cl2].3H2O complex were synthesized. The geometry of PFPFMI and its Zn(II) complex was described through CHN analyses, Fourier‐transform infrared spectroscopy (FTIR), UV–visible, X‐ray diffraction (XRD), thermal gravimetric analysis (TGA), and mass spectral data tests. The spectral data of the nano‐sized [Zn(PFPFMI)Cl2].3H2O complex indicates that the PFPFMI ligand functions as a tetradentate (N2O2) coordination through two azomethine nitrogen groups (N) and two furan ring oxygen (O) atoms. Density functional theory (DFT) calculations were performed using the molecular studio software to investigate the optimal geometry of PFPFMI and its [Zn(PFPFMI)Cl2].3H2O complex. The SEM, TEM, XRD, AFM, and energy dispersive X‐ray analysis (EDX) analyses of the studied complex unveil distinct and strong diffraction peaks, indicating its crystalline nature and providing evidence of its nano‐sized particle sizes. Additionally, the inhibition zone diameter was used to assess the in vitro antimicrobial action of PFPFMI and the particular complex against Gram‐positive bacteria Streptococcus pneumonia and Bacillus subtilis, Gram‐negative bacteria Pseudomonas aeruginosa, Salmonella typhi, and Escherichia coli, as well as fungi Aspergillus fumigatus, Geotricum candidum, Syncephalastrum racemosum, and Candida tropicalis. The [Zn(PFPFMI)Cl2].3H2O complex exhibits higher activity than the ligand PFPFMI. In vitro cytotoxicity of the synthesized [Zn(PFPFMI)Cl2].3H2O complex was explored using MCF7 (breast cancer), HCT116 (colon cancer), A549 (lung cancer), HePG‐2 (liver cancer), A375 (melanoma cancer), and normal lung fibroblast (WI38) cell lines. Based on IC50 and selective index (SI) values, it was shown that the complex exhibited higher potency against MCF7 cell lines. Moreover, the Zn(II) complex exhibited the ability to induce DNA damage in MCF7 cells, resulting in dose‐dependent cell apoptosis. Subsequent investigations revealed that complex 2 also induced cell cycle arrest in the G2 and S phases.

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

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