Normal Fibroblast Cells Research Articles

Anticancer Activity of 4-Aryl-1,4-Dihydropyridines

We have synthesized 22 symmetric and asymmetric 4-aryl-1,4-dihydropyridines (1,4-DHPs) by a “green” microwave-assisted one-pot multicomponent Hantzsch reaction and evaluated their cytotoxicity to three human cancer cell lines regarding U-251MG (human glioblastoma), HeLa 229 (human cervical adenocarcinoma), and MCF-7 (human breast carcinoma). None of the 1,4-DHPs were cytotoxic to U-251MG cells. Most of the 1,4-DHPs did not affect HeLa 229 or MCF-7 cell viability. On the other hand, symmetric 1,4-DHPs 18 (diethyl 4-(4-benzyloxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate), 19 (diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate), and 20 (diethyl 4-(3-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) reduced the HeLa (IC50 = 3.6, 2.3, and 4.1 µM, respectively) and MCF-7 (IC50 = 5.2, 5.7, and 11.9 µM, respectively) cell viability. These 1,4-DHPs were more cytotoxic to the HeLa and MCF-7 cells than to the GM07492 (normal human fibroblast) cells, as evidenced by their selectivity indexes. Therefore,1,4-DHPs 18, 19, and 20 may serve as novel lead compounds to discover other 1,4-DHP derivatives with improved anticancer potency and selectivity.

A novel biosynthesis of activated carbon manganese oxide nanocomposite and assessment of the biomedical role in fabricated cotton fabric nanocomposite

Ordinary products undergo a transformation to imbue new functional characteristics through the incorporation of nanocomposites into textile fabrics due to their high surface-volume ratio. In the present research, activated carbon (AC) manganese oxide nanocomposite was prepared through the sonochemical method using almond leaves and incorporated into cotton fabric via ultrasonic and dip coating methods to enhance the antibacterial activity. The characterization of the nanocomposite was conducted using various techniques such as X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy,energy-dispersive X-ray spectroscopy, UV–vis spectroscopy, and photoluminescence spectroscopy. The photo luminescence spectra showed a predominant yellow emission at 572 nm. The AC-Mn3O4 nanocomposite exhibited excellent antibacterial activity against gram-positive and -negative bacteria. Notably, AC-Mn3O4 nanocomposite-loaded cotton fabric showed tremendous activity toward Staphylococcus and Escherichia coli bacteria. The antioxidant evaluation using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay revealed a higher antioxidant activity with a lower IC50 value. In vitro cytotoxicity of AC-Mn3O4 nanocomposite was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetazolium bromide (MTT) assay against normal mouse fibroblast cells(NIH3T3 cell line) at different concentrations with an IC50 value of 187.6 μg/ml. These results confirm the simple, nontoxic and eco-friendly protocol for the coating of AC-Mn3O4 nanocomposite on cotton fabric, which could be used as a safer alternative approach in health-care applications.

Niosome preparation of atorvastatin drug with green preparation approach for in-vitro study of transdermal absorption with lavender essential oil

Introduction: Studies have pointef to anti-inflammatory properties of atorvastatin. In this research, noisome nanoparticles have been used to increase skin penetration and drug retention. Method: Atorvastatin niosomes were prepared using the sonication method. The effect of cholesterol: surfactant mixture ratio was investigated on physicochemical properties of nanoparticles. Studies have been performed on the morphological features, and characterization of nanoparticles. The toxicity of optimal formulation was investigated on a normal human fibroblast cell line. Different percentages of lavender essential oil were added to the optimal formulation gel, and skin drug delivery studies were performed. Results: The optimal formulation had the optimum particle size, PDI, zeta potential, and EE%, which leads to higher stability and dissolution of atorvastatin in the body. Morphological studies conducted on properties of nanoparticles illustrated a spherical shape and no interference with other formulation components. No cytotoxicity was detected for improved formulation of nanoparticles, including atorvastatin. In-vitro skin permeation results indicated that gel containing 0.5% lavender essential oil atorvastatin noisome (Atrosome) could enhance the dermal delivery of atorvastatin where a higher concentration of atorvastatin can be detected in skin layers. Conclusion: As evidenced by the results of this study, preparing nanoparticles from atorvastatin and adding essential oil to the final formulation exerts a positive effect on local drug delivery. Moreover, drug delivery with nanocarriers significantly increased the percentage of drug retention in the target site.

Chemical Composition of Anabasis articulata, and Biological Activity of Greenly Synthesized Zinc Oxide Composite Nanoparticles (Zn-NPs): Antioxidant, Anticancer, and Larvicidal Activities

The synthesis of nanoparticles utilizing green techniques is becoming increasingly important due to its low cost, biocompatibility, high productivity, and eco-friendliness. Herein, the current work focused on the biosynthesis, characterization, and biological applications of zinc oxide nanoparticles (ZnO-NPs) from Anabasis articulata, including antioxidant anticancer and larvicidal properties, as well as modifications to the phytochemical ingredients. Hence, the tannin, phenolic, and flavonoid concentrations of the produced nanoparticle samples were lower than those of the original aqueous extract. When compared to the results of ascorbic acid (12.78 mg/mL), the produced extract of A. articulata and its zinc nanoparticles showed remarkable efficacy as antioxidant agents with IC50 values of 27.48 and 69.53 mg/mL, respectively. A normal lung fibroblast cell line (WI-38) and three tumor cells were used to test the compounds’ anticancer properties. With an IC50 of 21.19 µg/mL, the ZnO-NPs of A. articulata showed the greatest cytotoxicity against HePG-2 cell lines. Additionally, A. articulata zinc nanoparticles showed significant cytotoxicity against MCF-7 and PC3 tumor cell lines, with IC50 values of 30.91 and 49.32 µg/mL. The biogenic ZnO-NPs had LC50 and LC90 values of 13.64 and 26.23 mg/L, respectively, and are very effective against Aedes aegypti larval instar (III). Additionally, the percentages of larval mortality increased from 28.61% at 5 ppm to 84.69% at 25 ppm after 24 h post-treatment. The overall results of this study point to the potential of A. articulata as a substitute biological agent for potential therapeutic/leutic uses in the medical domains and for preventing the proliferation of malarial vector insects.

Green synthesized chitosan-coated iron oxide nanocomposite using Cissus quadrangularis plant extract for antibacterial, antioxidant and anticancer applications

Metal oxide nanoparticles (NPs) have demonstrated their potential to eliminate a wide range of drug-resistant bacterial pathogens and cancer cells in recent years. Iron oxide (Fe3O4) NPs have received significant attention due to their wide range of uses in the field of biomedicine. In specific, biopolymer-encapsulated Fe3O4 NPs were applied in cancer therapy owing to their biocompatibility and biodegradability. The current investigation describes a bio-inspired approach to synthesize chitosan-based Fe3O4 nanocomposite (NC) employing Cissus quadrangularis (CQ) plant extract in a sustainable manner. The physicochemical, morphological, compositional, surface texture and thermal stability properties of the biopolymer-coated nanocomposites were characterised using FT-IR, UV–vis, XRD, XPS, HR-SEM, TEM, TGA, BET and TGA analyses. The antibacterial efficacy was examined in strains of Escherichia coli and Staphylococcus aureus, which verified that the growth of bacterial pathogens was inhibited by a substantial increase in the concentration of composites. The DPPH assay results were utilized to assess the free radical scavenging activity. The in vitro anticancer activity was found to be significant against the human osteosarcoma (MG-63) cell line, with an IC50 value of 54 ± 0.50 μg/mL. The enhanced biocompatibility of NCs was confirmed by cytotoxic testing on human RBCs and normal L929 fibroblast cells.

Novel nano composites from Citrus limon and Citrullus colocynthis agricultural wastes for biomedical applications

In recent years, academic and industrial research has focused on using agro-waste for energy and new material production to promote sustainable development and lessen environmental issues. In this study, new nanocomposites based on polyvinyl alcohol (PVA)-Starch using two affordable agricultural wastes, Citrus limon peels (LP) and Citrullus colocynthis (Cc) shells and seeds powders with different concentrations (2, 5, 10, and 15 wt%) as bio-fillers were prepared. The nanocomposites were characterized by Dielectric Spectroscopy, Fourier-Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and water swelling ratio. The antimicrobial properties of the nanocomposites against Escherichia coli, Staphylococcus aureus, and Candida albicans were examined to investigate the possibility of using such composites in biomedical applications. Additionally, the biocompatibility of the composites on human normal fibroblast cell lines (HSF) was tested using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results demonstrate that the filler type and concentration strongly affect the film's properties. The permittivity ε′, dielectric loss ε″ and conductivity σdc increased by increasing filler content but still in the insulators range that recommend such composites to be used in the insulation purposes. Both bio fillers control the water uptake, and the samples filled with LP were more water resistant. The polyvinyl alcohol/starch incorporated with 5 wt% LP and Cc have antimicrobial effects against all the tested microorganisms. Increasing the filler content has a negative impact on cell viability.

Targeting PRMT5 enhances the radiosensitivity of tumor cells grown in vitro and in vivo

PRMT5 is a widely expressed arginine methyltransferase that regulates processes involved in tumor cell proliferation and survival. In the study described here, we investigated whether PRMT5 provides a target for tumor radiosensitization. Knockdown of PRMT5 using siRNA enhanced the radiosensitivity of a panel of cell lines corresponding to tumor types typically treated with radiotherapy. To extend these studies to an experimental therapeutic setting, the PRMT5 inhibitor LLY-283 was used. Exposure of the tumor cell lines to LLY-283 decreased PRMT5 activity and enhanced their radiosensitivity. This increase in radiosensitivity was accompanied by an inhibition of DNA double-strand break repair as determined by γH2AX foci and neutral comet analyses. For a normal fibroblast cell line, although LLY-283 reduced PRMT5 activity, it had no effect on their radiosensitivity. Transcriptome analysis of U251 cells showed that LLY-283 treatment reduced the expression of genes and altered the mRNA splicing pattern of genes involved in the DNA damage response. Subcutaneous xenografts were then used to evaluate the in vivo response to LLY-283 and radiation. Treatment of mice with LLY-283 decreased tumor PRMT5 activity and significantly enhanced the radiation-induced growth delay. These results suggest that PRMT5 is a tumor selective target for radiosensitization.

Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study

BackgroundThe wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated.MethodsIn the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed.ResultsThe HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure.ConclusionsThis study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

EVALUATION OF IN-VITRO ANTIMICROBIAL ANTIOXIDANT AND ANTICANCER ACTIVITY OF A NEW CARBOXYMETHYLCHITOSAN-BASED CYANOGUANIDINE COPOLYMER

A new carboxymethylchitosan-based acryloylcyanoguanidine copolymer (CMCS-g-ACG) has been successfully prepared using the grafting technique. The grafting percentage, grafting efficiency, and homopolymer percentage were 86, 85, and 14%, respectively. The chemical structure and surface morphology of the CMCS-g-ACG copolymer were confirmed using elemental analysis, FTIR, 1H-NMR, XRD, and SEM. The copolymer has greater inhibition activity on both Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Candida albicans (C. albicans) in comparison to CMCS. It is more potent against E. coli than S. aureus. At 2000 μg/mL concentration, CMCS and the copolymer exhibited DPPH scavenging of 63.45% ± 4.19 and 78.56% ± 4.61, respectively. The copolymer of concentration less than 62.5 μg/mL was safe on the normal human lung fibroblast cells. The growth inhibition of the breast cancer cells at 500 μg/mL was 79.59% ± 2.12 and 91.41% ± 2.34 for CMCS and the copolymer, respectively. Thus, the insertion of ACG into CMCS highly boosted its antimicrobial, antioxidant and anticancer characteristics. It is a proper strategy to realize good systems to compete the traditional drugs used for such applications.

Fibroblasts Promote Resistance to KRAS Silencing in Colorectal Cancer Cells.

Colorectal cancer (CRC) responses to KRAS-targeted inhibition have been limited due to low response rates, the mechanisms of which remain unknown. Herein, we explored the cancer-associated fibroblasts (CAFs) secretome as a mediator of resistance to KRAS silencing. CRC cell lines HCT15, HCT116, and SW480 were cultured either in recommended media or in conditioned media from a normal colon fibroblast cell line (CCD-18Co) activated with rhTGF-β1 to induce a CAF-like phenotype. The expression of membrane stem cell markers was analyzed by flow cytometry. Stem cell potential was evaluated by a sphere formation assay. RNAseq was performed in KRAS-silenced HCT116 colonospheres treated with either control media or conditioned media from CAFs. Our results demonstrated that KRAS-silencing up-regulated CD24 and down-regulated CD49f and CD104 in the three cell lines, leading to a reduction in sphere-forming efficiency. However, CAF-secreted factors restored stem cell marker expression and increased stemness. RNA sequencing showed that CAF-secreted factors up-regulated genes associated with pro-tumorigenic pathways in KRAS-silenced cells, including KRAS, TGFβ, NOTCH, WNT, MYC, cell cycle progression and exit from quiescence, epithelial-mesenchymal transition, and immune regulation. Overall, our results suggest that resistance to KRAS-targeted inhibition might derive not only from cell-intrinsic causes but also from external elements, such as fibroblast-secreted factors.

Investigating the effect of Fusobacterium nucleatum on the aggressive behavior of cancer-associated fibroblasts in colorectal cancer

Fusobacterium nucleatum, (F. nucleatum) as a known factor in inducing oncogenic, invasive, and inflammatory responses, can lead to an increase in the incidence and progression of colorectal cancer (CRC). Cancer-associated fibroblasts (CAF) are also one of the key components of the tumor microenvironment (TME), which lead to resistance to treatment, metastasis, and disease recurrence with their markers, secretions, and functions. This study aimed to investigate the effect of F. nucleatum on the invasive phenotype and function of fibroblast cells isolated from normal and cancerous colorectal tissue. F. nucleatum bacteria were isolated from deep periodontal pockets and confirmed by various tests. CAF cells from tumor tissue and normal fibroblasts (NF) from a distance of 10 cm of tumor tissue were isolated from 5 patients by the explant method and were exposed to secretions and ghosts of F. nucleatum. The expression level of two markers, fibroblast activation protein (FAP), and α-smooth muscle actin (α-SMA), and the amount of production of two cytokines TGF-β and IL-6 from fibroblast cells were measured by flow cytometry and ELISA test, respectively before and after exposure to different bacterial components. The expression of the FAP marker was significantly higher in CAF cells compared to NF cells (P < 0.05). Also, the expression of IL-6 in CAF cells was higher than that of NF cells. In investigating the effect of bacterial components on the function of fibroblastic cells, after comparing the amount of IL-6 produced between the normal tissue of each patient and his tumoral tissue under 4 treated conditions, it was found that the amount of IL-6 production from the CAF cells of patients in the control group, treated with heat-killed ghosts and treated with paraformaldehyde-fixed ghosts had a significant increase compared to NF cells (P < 0.05). Due to the significant increase in FAP marker expression in fibroblast cells of tumor tissue compared to normal tissue, it seems that FAP can be used as a very good therapeutic marker, especially in patients with high levels of CAF cells. Various components of F. nucleatum could affect fibroblast cells differentially and at least part of the effect of this bacterium in the TME is mediated by CAF cells.

Circular economy reinforcement through molecular fabrication of textile wastes with microbial synthesized ZnO nanoparticles to have multifunctional properties

The fibrous wastes generated from the mills of textile production can be recycled and converted into high add-values products to be implemented in several applications. The current study aimed to employ commercial free cellulase enzyme to partially hydrolyze (activate) the polyester cotton blended (PET/C) fibrous wastes by creation functional groups such as OH and COOH on their surfaces. The activated fibrous wastes were then modified by coating with ZnO nanoparticles (ZnO-NPs) biosynthesized by actinobacterial cultures free supernatant. The isolate was identified as Streptomyces pseudogriseolus with accession number of OR574241. The conditions that influence the actino-synthesis of ZnO-NPs were optimized and the product was characterized using spectroscopic vision, FTIR, XRD, TEM and SEM. The characteristic ZnO peaks were obviously observed by EDX analysis with 0.38 and 0.75% (wt%), respectively. TEM analyses proved the nanoscale of ZnO-NPs (5–15 nm) which was followed by cytotoxic evaluation for the produced NPs. Fortunately, the tested actino-ZnO-NPs didn’t have any cytotoxicity against human normal fibroblast cell line (BJ1), which means that the product can be safely used in a direct-contact with human skin. The treated PET/C blended waste fabrics coated with ZnO-NPs showed high antimicrobial activity and ultraviolet protection values after functionalization by cellulase. EDX analysis demonstrates the presence of Zn peaks on the coated fabrics compared with their absence in blank and control samples, while SEM images showed the formation of a thin layer of ZnO-NPs on the fabric surface. The obtained smart textile can be applied several needed sectors.

New pyridopyrimidine derivatives as dual EGFR and CDK4/cyclin D1 inhibitors: synthesis, biological screening and molecular modeling.

Aim: A series of pyridopyrimidine derivatives 5-20 was designed, synthesized and examined for antitumor activity using four types of malignant cells.Materials & methods: Cervical cancer (HeLa), hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-166) cells, as well as normal human lung fibroblast cells (WI-38) were used to determine the cytotoxicity.Results: Pyrazol-1-yl pyridopyrimidine derivative 5 was found to be the most active compound against three malignant cells Hela, MCF-7 and HepG-2 with IC50 values of 9.27, 7.69 and 5.91μM, respectively, related to standard Doxorubicin. Moreover, compounds 5 and 10 showed good inhibition against cyclin dependent kinase (CDK4/cyclin D1) and epidermal growth factor (EGFR) enzymes.

Antibacterial, mosquito larvicidal, and cytotoxicity potential of AgNPs synthesized using Pittosporum undulatum under in vitro conditions

In this study, the phytochemical profile and silver nanoparticle (AgNPs)-synthesizing ability of Pittosporum undulatum methanol extract were investigated. Furthermore, biological applications of the AgNPs, such as antibacterial effect (against Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis, and Escherichia coli), mosquito larvicidal effect (against Anopheles stephensi, Culex quinquefasciatus, and Aedes aegypti), and cytotoxicity (against fibroblast cell line L929) were evaluated using in vitro experiments. The phytochemical analysis revealed that the methanol extract contained cardiac glycosides, terpenoids, saponins, alkaloids, flavonoids, glycosides, coumarins, phenolics, and tannins. Furthermore, standard characterization techniques such as UV–Vis spectrometry, SEM, TEM, FTIR, and XRD confirmed that the methanol extract of P. undulatum effectively synthesized the AgNPs. The synthesized AgNPs had a spherical shape and size of 20–200 nm. The bactericidal analysis revealed that the AgNPs have dose-dependent antibacterial activity. The MTT assay showed that the AgNPs were bio-compatible up to a dosage of 250 μg mL−1 in the normal fibroblast cell line L929. Furthermore, the LC50 values for AgNPs against larvae of An. stephensi, Cx. quinquefasciatus, and Ae. aegypti were 0.4, 4.7, and 1.2 ppm, respectively. Field trials demonstrated that the larvicidal effect was enhanced within 24–72 h, and the rate of reduction increased over time. Thus, our findings provide an ideal sustainable AgNP bio-pesticide to combat filarial, dengue, and malaria vectors.

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.