Human Colorectal Adenocarcinoma Cell Line Research Articles

Development and Assessment of 1,5-Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK-2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a-j, 8a-j, 9a-c, and 10a-c. The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d, 8g, 8i, and 10c inhibited EGFR with IC50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d, 8g, 8i, and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.

Extraction yield and biological activity of phycobiliproteins from Porphyridium purpureum using atmospheric cold plasma discharge and jet systems

Phycobiliproteins (PBPs) extracted from Porphyridium purpureum (P.p) have bioactive properties and are widely used as ingredients in nutraceutical and food applications. This study investigated the use of two cold plasma systems, namely cold plasma discharge system (CPDS) and cold plasma jet system (CPJS), for the aqueous extraction of PBPs from P. p. Three types of PBPs, namely phycoerythrin (PE), phycocyanin (PC) and allophycocyanin (APC) were identified in the crude extracts obtained. The highest PBPs extraction yield (11.31 ± 1.02 mg/g DW P. p) was obtained from CPDS treated samples at 25 kV using N2 for 9 min. CPDS treatments were also shown to be more effective than CPJS treatments in increasing antioxidant activities of the PBPs crude extracts obtained. PBPs crude extracts obtained using CPDS (25 kV; 6 min; N2) had the highest DPPH (69.44 ± 0.10%) and FRAP (207.34 ± 12.96 μmol/L) antioxidant activities observed. PBPs obtained from samples treated with CPDS (25 kV; 9 min; N2) exhibited the highest cytotoxicity potential in Caco-2 human colorectal adenocarcinoma cell lines. This study demonstrates that cold plasma treatments increase the extraction yield of PBPs obtained from P. p and also enhance antioxidant and cytotoxic properties of the PBP crude extracts. However, an increase in treatment time beyond 6 min for both plasma systems was shown to reduce the level of antioxidant activity in PBPs.

Biosynthesis, characterization, and investigation of antimicrobial and cytotoxic activities of silver nanoparticles using Solanum tuberosum peel aqueous extract

Metallic nanoparticle biosynthesis is thought to offer opportunities for a wide range of biological uses. The green process of turning biological waste into utilizable products gaining attention due to its economical and eco-friendly approach in recent years. This study reported the ability of Solanum tuberosum (ST) peel extract to the green synthesis of non-toxic, stable, small-sized silver nanoparticles without any toxic reducing agent utilizing the phytochemical components present in its structure. UV–visible spectroscopy, X-ray diffraction analysis, Fourier transform infrared spectroscopy, flourier scanning electron microscopy, atomic force microscopy, transmission electron microscopy, and energy dispersive analysis X-ray confirmed the biosynthesis and characterization of silver nanoparticles. Also, dynamic light scattering and thermogravimetric analyses showed stable synthesized nanoparticles. The antibacterial activity of the biosynthesized silver nanoparticles was evaluated against four different bacterial strains, Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus) Bacillus subtilis (B. subtilis), and a yeast, Candida albicans (C. albicans) using the minimum inhibitory concentration technique. The cytotoxic activities were determined against Human dermal fibroblast (HDF), glioblastoma (U118), colorectal adenocarcinoma (CaCo-2), and human ovarian (Skov-3) cell lines cancer cells using MTT test. The nanoparticle capping agents that could be involved in the reduction of silver ions to Ag NPs and their stabilization was identified using FTIR. Nanoparticles were spherical in shape and had a size ranging from 3.91 to 27.07 nm, showed crystalline nature, good stability (−31.3 mV), and the presence of capping agents. ST-Ag NPs significantly decreased the growth of bacterial strains after treatment. The in vitro analysis showed that the ST-Ag NPs demonstrated dose-dependent cytotoxicity against cell lines. Based on the data, it is feasible to infer that biogenic Ag NPs were capped with functional groups and demonstrated considerable potential as antibacterial and anticancer agents for biomedical and industrial applications.

Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

AbstractThe nine new imidazole‐hydrazone derivatives of Schiff base were synthesized from the condensation reactions of 1‐methyl‐1H‐imidazole‐2‐carbaldehyde with various substituted‐hydrazide derivatives. Structures of the final compounds (1 a–1 i) were characterized by using 1H NMR, 13C NMR spectroscopic techniques, elemental analysis, and crystal X‐ray diffraction. The in vitro carbonic anhydrase I and II potentials of these synthesized were evaluated. The result suggests that compound 1 a, a 4‐methoxy substituted analog with an IC50 of 0.949 μM, was found to have the most potent hCA I inhibitory activity. Compounds 1 c, 1 d, and 1 h were the most potent compounds on hCA II with IC50 values of 3.330, 4.454, and 5.66 μM, respectively. All compounds were examined for their cytotoxicity towards human colorectal adenocarcinoma cell (HT29) and rat glioma cell line (C6) compared to mouse fibroblast normal cell line (L929) using the MTT assay method. The compounds 1 a, 1 d, and 1 i exhibited significant antiproliferative activity with less toxicity to a health cell line. Consequently, compound 1 a could be the potential lead for emerging selective cytotoxic compounds directing hCA I. Compound 1 d could be the potential lead for emerging selective cytotoxic compounds directing hCA II.

In Vitro Analysis of the Effect of SARS-CoV-2 Non-VOC and four Variants of Concern on MHC-Class-I Expression on Calu-3 and Caco-2 Cells.

As the MHC-I-pathway is key to antigen presentation to cytotoxic T-cells and, therefore, recognition by the host adaptive immune system, we hypothesized that SARS-CoV-2 including its Variants of Concern (VOCs), influences MHC-I expression on epithelial cell surfaces as an immune evasion strategy. We conducted an in vitro time course experiment with the human airway epithelial cell line Calu-3 and the human colorectal adenocarcinoma cell line Caco-2. Cells were infected with SARS-CoV-2 strains non-VOC/B.1.1, Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, and Delta/B.1.617.2. At 2, 24, 48 and 72 h post-infection we performed RT-qPCR to track viral replication. Simultaneously, we performed intracellular staining with a serum of a double-vaccinated healthy adult containing a high amount of spike protein antibody. In flow cytometry experiments, we differentiated between infected (spike protein positive) and bystander (spike protein negative) cells. To compare their HLA expression levels, cells were stained extracellularly with anti-HLA-A-IgG and anti-HLA-B,C-IgG. While HLA-A expression was stable on infected Calu-3 cells for all variants, it increased to different degrees on bystander cells in samples infected with VOCs Beta, Gamma, Delta, or non-VOC over the time course analyzed. In contrast, HLA-A levels were stable in bystander Calu-3 cells in samples infected with the Alpha variant. The upregulation of MHC-I on spike protein negative bystander cells in Calu-3 cell cultures infected with Beta, Gamma, Delta, and partly non-VOC might suggest that infected cells are still capable of secreting inflammatory cytokines like type-I interferons stimulating the MHC-I expression on bystander cells. In comparison, there was no distinct effect on HLA expression level on Caco-2 cells of any of the VOCs or non-VOC. Further investigations of the full range of immune evasion strategies of SARS-CoV-2 variants are warranted.

Combination of CNTs with Classical Drugs for Treatment in Human Colorectal Adenocarcinoma (HT-29) Cell Line.

Due to the increase in new types of cancer cells and resistance to drugs, conventional cancer treatments are sometimes insufficient. Therefore, an alternative is to apply nanotechnology to biomedical areas, minimizing side effects and drug resistance and improving treatment efficacy. This work aims to find a promising cancer treatment in the human colorectal adenocarcinoma cell line (HT-29) to minimize the viability of cells (IC50) by using carbon nanotubes (CNTs) combined with different drugs (5-fluorouracil (5-FU) and two repurposing drugs-tacrine (TAC) and ethionamide (ETA). Several CNT samples with different functional groups (-O, -N, -S) and textural properties were prepared and characterized by elemental and thermogravimetry analysis, size distribution, and textural and temperature programmed desorption. The samples that interacted most with the drugs and contributed to improving HT-29 cell treatment were samples doped with nitrogen and sulfur groups (CNT-BM-N and CNT-H2SO4-BM) with IC50 1.98 and 2.50 µmol∙dm-3 from 5-FU and 15.32 and 15.81 µmol∙dm-3 from TAC. On the other hand, ETA had no activity, even combined with the CNTs. These results allow us to conclude that the activity was improved for both 5-FU and TAC when combined with CNTs.

Increased Production of Interleukin-10 and Decreased Production of Tumor Necrosis Factor-α by Lacticaseibacillus rhamnosus PL60

Lacticaseibacillus rhamnosus PL60, originally isolated from healthy baby feces, has beneficial activities including resistance to acid and bile acids, immune-enhancing activity, inhibition of various intestinal pathogens, anti-oxidation activity, adherence to the intestines, susceptibility to antimicrobials, an anti-obesity effect, and an anti-fatty liver effect. In the present study, the binding activity of L. rhamnosus PL60 to the HT-29 human colorectal adenocarcinoma cell line and mouse intestines was established. L. rhamnosus PL60 increased interleukin-10 production and decreased tumor necrosis factor-α production in a dose-dependent manner in HT-29 cells treated with lipopolysaccharide. Similar results were observed in an in vivo experiment with BALB/c mice fed with L. rhamnosus PL60. Taken together, results from previous studies and the present study establish that L. rhamnosus PL60 is a probiotic candidate for inflammation-related diseases.

Fluorinated Benzofuran and Dihydrobenzofuran as Anti-Inflammatory and Potential Anticancer Agents.

Benzofuran and 2,3-dihydrobenzofuran scaffolds are heterocycles of high value in medicinal chemistry and drug synthesis. Targeting inflammation in cancer associated with chronic inflammation is a promising therapy. In the present study, we investigated the anti-inflammatory effects of fluorinated benzofuran and dihydrobenzofuran derivatives in macrophages and in the air pouch model of inflammation, as well as their anticancer effects in the human colorectal adenocarcinoma cell line HCT116. Six of the nine compounds suppressed lipopolysaccharide-stimulated inflammation by inhibiting the expression of cyclooxygenase-2 and nitric oxide synthase 2 and decreased the secretion of the tested inflammatory mediators. Their IC50 values ranged from 1.2 to 9.04 µM for interleukin-6; from 1.5 to 19.3 µM for Chemokine (C-C) Ligand 2; from 2.4 to 5.2 µM for nitric oxide; and from 1.1 to 20.5 µM for prostaglandin E2. Three novel synthesized benzofuran compounds significantly inhibited cyclooxygenase activity. Most of these compounds showed anti-inflammatory effects in the zymosan-induced air pouch model. Because inflammation may lead to tumorigenesis, we tested the effects of these compounds on the proliferation and apoptosis of HCT116. Two compounds with difluorine, bromine, and ester or carboxylic acid groups inhibited the proliferation by approximately 70%. Inhibition of the expression of the antiapoptotic protein Bcl-2 and concentration-dependent cleavage of PARP-1, as well as DNA fragmentation by approximately 80%, were described. Analysis of the structure-activity relationship suggested that the biological effects of benzofuran derivatives are enhanced in the presence of fluorine, bromine, hydroxyl, and/or carboxyl groups. In conclusion, the designed fluorinated benzofuran and dihydrobenzofuran derivatives are efficient anti-inflammatory agents, with a promising anticancer effect and a combinatory treatment in inflammation and tumorigenesis in cancer microenvironments.

Optimization of parameters for stir-frying of Kansui Radix with vinegar based on conversion of toxic components

This study aims to optimize the parameters for stir-frying of Kansui Radix with vinegar based on the conversion of representative toxic diterpenes, which is expected to serve as a reference for the standardized production of Kansui Radix stir-fried with vinegar. To be specific, the toxic components [3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol(3-O-EZ), kansuiphorin C(KPC)] in Kansui Radix and the products(ingenol, 20-deoxyingenol) after the stir-frying with vinegar were selected. The toxicity to intestine and water-draining activity were evaluated with NCM460(normal human colon mucosal epithelial cell line) and HT-29(a human colorectal adenocarcinoma cell line). An HPLC method was then developed to assess the conversion of toxic components. On this basis, temperature, time, and amount of vinegar for the processing of Kansui Radix were optimized with the Box-Behnken design and the content of ingenol and 20-deoxyingenol as evaluation index. The results showed that after the stir-frying of Kansui Radix with vinegar, 3-O-EZ and KPC were first converted to monoester 3-O-(2'E,4'Z-decadienoyl)ingenol(3-EZ) and 5-O-benzoyl-20-deoxyingenol(5-O-Ben) and finally to almost non-toxic ingenol and 20-deoxyingenol, respectively. Meanwhile, the water-draining activity was retained. Six compounds had a good linear relationship with the peak area in the corresponding concentration ranges(R~2≥0.999 8), and the average recovery fell in the range of 98.20%-102.3%(RSD≤2.4%). The content of representative diterpenes and intermediate products was 14.78%-24.67% lower in the Kansui Radix stir-fried with vinegar than in the Kansui Radix, while the content of the conversed products was 14.37%-71.37% higher. Among the process parameters, temperature had significant influence on the total content of products, followed by time. The optimal parameters were 210 ℃, 15 min, and 30% vinegar. The relative error between the experimental results and the predicted values was 1.68%, indicating that the process was stable and reproducible. The strategy of screening optimal parameters for stir-frying of Kansui Radix with vinegar based on the transformation of toxic components can help improve the production stability, reduce the toxicity, and ensure the efficacy of Kansui Radix stir-fried with vinegar, which can serve as a reference for the process optimization of similar toxic Chinese medicinals.

Optimization of process factor and characterization of vinegar-like beverage production via spontaneous fermentation from pineapple peel waste

A feasible approach to compensating for pineapple wastage is by utilizing the waste. In the present study, pineapple peels were subjected to spontaneous fermentation to produce a vinegar-like beverage. Based on the central composite design (CCD) approach, optimization of the process factor recorded a maximum total acid yield, Yp/s, and total acidity of 0.49 and 3.03%, respectively. Furthermore, the beverage possessed increased tartaric, citric, ascorbic, acetic, and ferulic acids at a maximum of 1.196%. The cytotoxicity activity toward the human colorectal adenocarcinoma cell line documented a half maximal inhibitory concentration (IC50) at 3.4% v/v of the beverage. This study showcased optimized vinegar-like beverage production by indigenous microorganisms (IMO) with pineapple peel. The beverage contained improved organic and phenolic acids contents and antioxidant potential, which could be employed as a possible human colorectal cancer cure.

Biotransformation of white and black mustard grains through germination and enzymatic hydrolysis revealed important metabolites for antioxidant properties and cytotoxic activity against Caco-2 cells

Germination and enzymatic hydrolysis are biological processes with well-recognized positive effects on phenolic composition and antioxidant potential. This study aimed to apply those processes to white (Sinapsis alba) and black (Brassica nigra) mustard grains and to analyze the influences on the total phenolic content (TPC); phenolic and peptide profile determined by ultra-performance liquid chromatography–high resolution mass spectrometry (UPLC-HRMS); antioxidant potential (DPPH, ABTS, and FRAP assays); and cytotoxicity against Caco-2, a human colorectal adenocarcinoma cell line. Enzyme combinations for hydrolysis were different for each mustard grain, but for both species, enzymatic hydrolysis and germination showed a positive effect on antioxidant properties. From UPLC-HRMS analysis and molecular network studies, 14 peptides and 17 phenolic compounds were identified as metabolites released from mustard after processes application, which were strongly correlated with increased antioxidant activity. In addition, enzymatic hydrolysis applied in germinated mustard grains for both mustards increased the cytotoxic activity against Caco-2 human colorectal adenocarcinoma cell line.

Physicochemical characterization and cancer cell antiproliferative effect of silver-doped magnesia nanoparticles

Silver-doped magnesia nanoparticles (Ag/MgO) were synthesized using the precipitation method and characterized by various techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), Brunner-Emmett-Teller (BET) surface area measurements, and dispersive X-ray spectroscopy (EDX). The morphology of Ag/MgO nanoparticles was determined by transmission and scanning electron microscopy, which revealed cuboidal shaped nanoparticles with sizes ranging from 31 to 68 nm and an average size of 43.5 ± 10.6 nm. The anticancer effects of Ag/MgO nanoparticles were evaluated on human colorectal (HT29) and lung adenocarcinoma (A549) cell lines, and their caspase-3, -8, and -9 activities, as well as Bcl-2, Bax, p53, cytochrome C protein expressions were estimated. Ag/MgO nanoparticles showed selective toxicity towards HT29 and A549 cells while remaining relatively innocuous towards the normal human colorectal, CCD-18Co, and lung, MRC-5 cells. The IC50 values of Ag/MgO nanoparticles on the HT29 and A549 cells were found to be 90.2 ± 2.6 and 85.0 ± 3.5 μg/mL, respectively. The Ag/MgO nanoparticles upregulated caspase-3 and -9 activities, downregulated Bcl-2, upregulated Bax and p53 protein expressions in the cancer cells. The morphology of the Ag/MgO nanoparticle treated HT29 and A549 cells was typical of apoptosis, with cell detachment, shrinkage, and membrane blebbing. The results suggest that Ag/MgO nanoparticles induce apoptosis in cancer cells and exhibit potential as a promising anticancer agent.

In Vitro Cytotoxic Potential of Selected Jordanian Flora and Their Associated Phytochemical Analysis.

Traditional medicines are a significant source of phytochemicals with potential anticancer effects. Ten Jordanian plants were chosen to be tested for cytotoxicity on human colorectal (HT-29) and breast adenocarcinoma (MCF-7) cell lines. The ethanol extracts were screened for their potential cytotoxic effects using a Sulforhodamine B (SRB) colorimetric assay, using doxorubicin as positive control. Plants extracts exhibiting marked cytotoxic activity were further investigated by qualitative and quantitative phytochemical methods. Total phenolics were quantified using the Folin-Ciocalteu reagent, while flavonoids were quantified using aluminum chloride. The total saponins of the n-butanol fraction were estimated using diosgenin as a standard. The total alkaloids and total terpenoids were also evaluated using the gravimetric method. As results, Senecio leucanthemifolius (IC50: 13.84 μg/mL) and Clematis cirrhosa (IC50: 13.28 μg/mL) exhibited marked cytotoxic effects on human colorectal adenocarcinoma (HT-29) cell lines. Total phenolics, flavonoids, saponins, alkaloids, and terpenoids found in Senecio leucanthemifolius were (91.82, 14.90, 14.27, 101, and 135.4 mg/g of dry extract), respectively. They were revealed to be (68.18, 7.16, 31.25, 73.6, and 180 mg/g of dry extract) in Clematis cirrhosa, respectively. Senecio leucanthemifolius and Clematis cirrhosa have been found to possess cytotoxicity against colorectal (HT-29). In conclusion, the findings of this study offer a new perspective on Jordanian plant extracts anticancer activity research.

Green Synthesized Gold and Silver Nanoparticles Increased Oxidative Stress and Induced Cell Death in Colorectal Adenocarcinoma Cells.

The research investigated the effect of gold (Au-CM) and silver nanoparticles (Ag-CM) phytoreduced with Cornus mas fruit extract (CM) on a human colorectal adenocarcinoma (DLD-1) cell line. The impact of nanoparticles on the viability of DLD-1 tumor cells and normal cells was evaluated. Oxidative stress and cell death mechanisms (annexin/propidium iodide analysis, caspase-3 and caspase-8 levels, p53, BCL-2, BAX, NFkB expressions) as well as proliferation markers (Ki-67, PCNA and MAPK) were evaluated in tumor cells. The nanoparticles were characterized using UV-Vis spectroscopy and transmission electron microscopy (TEM) and by measuring zeta potential, hydrodynamic diameter and polydispersity index (PDI). Energy dispersive X-ray (EDX) and X-ray powder diffraction (XRD) analyses were also performed. The nanoparticles induced apoptosis and necrosis of DLD-1 cells and reduced cell proliferation, especially Ag-CM, while on normal cells, both nanoparticles maintained their viability up to 80%. Ag-CM and Au-CM increased the expressions of p53 and NFkB in parallel with the downregulation of BCL-2 protein and induced the activation of caspase-8, suggesting the involvement of apoptosis in cell death. Lipid peroxidation triggered by Ag-CM was correlated with tumor cell necrosis rate. Both nanoparticles obtained with phytocompounds from the CM extract protected normal cells and induced the death of DLD-1 tumor cells, especially by apoptosis.

Design, Synthesis, Characterization, and Evaluation of the Anti-HT-29 Colorectal Cell Line Activity of Novel 8-Oxyquinolinate-Platinum(II)-Loaded Nanostructured Lipid Carriers Targeted with Riboflavin.

Colorectal cancer is occasionally called colon or rectal cancer, depending on where cancer begins to form, and is the second leading cause of cancer death among both men and women. The platinum-based [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) compound has demonstrated encouraging anticancer activity. Three different systems of 8-QO-Pt-encapsulated nanostructured lipid carriers (NLCs) with riboflavin (RFV) were investigated. NLCs of myristyl myristate were synthesized by ultrasonication in the presence of RFV. RFV-decorated nanoparticles displayed a spherical shape and a narrow size dispersion in the range of 144-175 nm mean particle diameter. The 8-QO-Pt-loaded formulations of NLC/RFV with more than 70% encapsulation efficiency showed sustained in vitro release for 24 h. Cytotoxicity, cell uptake, and apoptosis were evaluated in the HT-29 human colorectal adenocarcinoma cell line. The results revealed that 8-QO-Pt-loaded formulations of NLC/RFV showed higher cytotoxicity than the free 8-QO-Pt compound at 5.0 µM. All three systems exhibited different levels of cellular internalization. Moreover, the hemotoxicity assay showed the safety profile of the formulations (less than 3.7%). Taken together, RFV-targeted NLC systems for drug delivery have been investigated for the first time in our study and the results are promising for the future of chemotherapy in colon cancer treatment.

Polystyrene Microplastics of Varying Sizes and Shapes Induce Distinct Redox and Mitochondrial Stress Responses in a Caco-2 Monolayer.

Currently, we lack crucial knowledge on how the physicochemical properties of particles affect cellular health, resulting in an important gap in our understanding of the human toxicity of microplastics (MPs). Our aim was to evaluate the impact of the size and the shape of MPs on uptake and the intracellular effects in a human epithelial colorectal adenocarcinoma (Caco-2) cell line. Spherical (200 nm and 2 µm) and fibre-/fragment-shaped (8.9 ± 10.1 µm by 1.14 ± 0.97 µm) polystyrene microplastics (PS-MPs) were used to study their uptake and the potential to induce redox and mitochondrial stress responses after 24 h of exposure. We demonstrated the cellular uptake of both spherical and fibre-/fragment-shaped MPs in a size-dependent manner. In response to 2 µm spheres, we observed differential expressions of redox-related genes, including HMOX1, CAT, and GPX1. All PS-MPs decreased the intracellular H2O2 levels, which can be attributed to mitochondrial stress responses, such as increased mitochondrial DNA content, footprint, and morphology. Altogether, we demonstrated uptakes and changes in redox and mitochondrial parameters for all PS-MPs, with the 200 nm spheres showing the most profound effects. This suggests that the induction of defensive responses in Caco-2 cells mainly correlates with the number of particles taken up.

Biocompatible Film‐Coating of Magnetic Soft Robots for Mucoadhesive Locomotion

AbstractMagnetically‐actuated soft robots for medical applications are required to be functional, biocompatible, as well as capable of robust motion inside human organs. In this paper, a ring‐shaped magnetic soft robot, with a flexible biopolymeric film coating, capable of motion on mucus‐coated surfaces is designed and investigated. The biopolymeric film made from chitosan–glycerol (C–G) solution endows the robot with robust locomotion capabilities on surfaces of diverse geometrical shapes and orientations. By utilizing mucoadhesive locomotion, the robot has the potential to carry out clinical procedures on enclosed mucus‐coated tissue surfaces. Material characterization shows that the mucoadhesion increases with the increase of contact times and/or preload forces. The softness of the C–G film can be adjusted by controlling the concentration of glycerol. The ring‐shaped design and magnetization profile decouple the locomotion and functions of the robot. Additionally, the C–G film‐coated robot is tested to be biocompatible for a human colorectal adenocarcinoma cell line with epithelial morphology (HT29). The C–G film reduces the negative effects (superoxide generation) of ferromagnetic particles. Three robot functions including pick‐and‐place, cargo transportation, and liquid capsule release are demonstrated on different surfaces to show the maneuverability, functionality, and potential of implementing clinical procedures through mucoadhesion.

The Potential Inhibitory Role of Acetyl-L-Carnitine on Proliferation, Migration, and Gene Expression in HepG2 and HT29 Human Adenocarcinoma Cell Lines.

Malignancies of the liver and colon are the most prevalent forms of digestive system cancer globally. Chemotherapy, one of the most significant treatments, has severe side effects. Chemoprevention using natural or synthetic medications can potentially reduce cancer severity. Acetyl-L-carnitine (ALC) is an acetylated derivative of carnitine essential for intermediate metabolism in most tissues. This study aimed to investigate the effects of ALC on the proliferation, migration, and gene expression of human liver (HepG2) and colorectal (HT29) adenocarcinoma cell lines. The cell viability and half maximal inhibitory concentration of both cancer cell lines were determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Wound healing after treatment was assessed using a migration assay. Morphological changes were imaged using brightfield and fluorescence microscopy. Post treatment, apoptotic DNA was detected using a DNA fragmentation assay. The relative mRNA expressions of matrix metallopeptidase 9 (MMP9) and vascular endothelial growth factor (VEGF) were evaluated using RT-PCR. The results showed that ALC treatment affects the wound-healing ability of HepG2 and HT29 cell lines. Changes in nuclear morphology were detected under fluorescent microscopy. ALC also downregulates the expression levels of MMP9 and VEGF in HepG2 and HT29 cell lines. Our results indicate that the anticancer action of ALC is likely mediated by a decrease in adhesion, migration, and invasion.

Silybin Showed Higher Cytotoxic, Antiproliferative, and Anti-Inflammatory Activities in the CaCo Cancer Cell Line while Retaining Viability and Proliferation in Normal Intestinal IPEC-1 Cells.

The anticancer potential of silymarin is well known, including its anti-inflammatory as well as antiproliferative effect mediated by influencing the cell cycle, suppression of apoptosis, and inhibition of cell-survival kinases. However, less is known about silybin, the main component of the silymarin complex, where studies indicate its dual effect on the proliferation and immune response of various cell types in a dose-dependent manner. Moreover, there is a lack of studies comparing the effect of silybin on the same type of healthy and tumor cells, especially intestinal ones. Therefore, our study aimed to investigate the concentration-dependent effect of silybin on the normal intestinal porcine epithelial cell line-1 (IPEC-1) and the human epithelial colorectal adenocarcinoma cell line (CaCo-2). The metabolic viability, cell cycle, mitochondrial membrane potential, apoptosis, and the relative gene expression for pro- and anti-inflammatory cytokines were monitored in cells treated with silybin. Silybin stimulates metabolic viability as well as proliferation in IPEC-1 cells, protects the mitochondrial membrane, and thus exerts a cytoprotective effect, and has only a minimal effect on the gene expression of pro-inflammatory cytokines but significantly increases the expression of anti-inflammatory TGF-β. In contrast, it inhibits metabolic viability in tumor intestinal CaCo-2 cells, has an antiproliferative effect accompanied by increased apoptosis, and significantly reduces the expression of genes for pro-inflammatory interleukins as well as TGF-β. The antiproliferative and anti-inflammatory effect of silybin on tumor intestinal cells without a negative effect on healthy cells is a prerequisite for its potential use in the adjuvant therapy of colon cancer; however, further studies are necessary.

Bio-Functional Activities of Tuscan Bee Pollen.

Bee pollen represents one of the most complete natural foods playing an important role in the diet for its health qualities and therapeutic properties. This work aimed to characterize a Tuscan bee pollen by evaluating its phytochemical profile and the in vitro and ex vivo antioxidant activities. The isolation and taxonomic and functional characterization of yeasts in the sample has been also conducted. Finally, the pollen anti-inflammatory potential has been assessed on a TNFα-inflamed human colorectal adenocarcinoma cell line (HT-29). Our results highlighted a good phytochemical composition in terms of polyphenols, flavonoids, flavonols, monomeric anthocyanins, and carotenoids. In addition, we detected good antioxidant activity and radical scavenging capacity by in vitro and ex vivo assays, as well as good antioxidant activity by isolated yeasts. Data showed no cytotoxic effects of bee pollen extracts, with average viability values >80% at each tested dose. Moreover, TNFα treatment did not affect HT-29 viability while upregulating IL-8, COX-2, and ICAM-1 gene expression, otherwise reduced by both doses of bee pollen. In conclusion, our sample represents an interesting functional food and a potential probiotic product, having high phytochemical compound levels and good antioxidant activities, as well as anti-inflammatory effects on the TNFα-inflamed HT-29 cell line.