HCT116 Human Colon Cancer Cells Research Articles

Novel Schiff bases of quinolin-4(1h)-one: Synthesis, antiproliferative evaluation, apoptosis, cell cycle, autophagy and molecular docking studies in human colon cancer cells

A green and efficient ultrasound-mediated protocol was developed for the synthesis of a series of novel Schiff bases derived from quinoline-4-one. The synthetic strategy involved the condensation of 4-oxo-1,4-dihydro-quinoline-3-carboxaldehyde with diverse anilines and heteroaryl amines. The synthesized compounds were characterized using spectroscopic techniques. A comprehensive in vitro cytotoxicity evaluation against HCT116 and HT-29 human colon cancer cell lines revealed that several compounds exhibited potent anticancer activity. Notably, compounds 3c and 3e demonstrated superior cytotoxicity compared to the clinical standard doxorubicin. Mechanistic studies indicated that these lead compounds induced apoptosis, necrosis, and cell cycle arrest at G1 and G2 phases. Furthermore, autophagy induction was observed. In silico ADMET predictions support the potential of compounds 3c and 3e as promising anticancer drug candidates. The molecular docking studies revealed that the Schiff bases 3c and 3e displayed good interaction with VEGFR-2 receptor. These findings underscore the quinoline-4-one scaffold as a valuable template for the development of novel antitumor agents.

The Inhibitory Effect and Mechanism of the Histidine-Rich Peptide rAj-HRP from Apostichopus japonicus on Human Colon Cancer HCT116 Cells.

Colon cancer is a common and lethal malignancy, ranking second in global cancer-related mortality, highlighting the urgent need for novel targeted therapies. The sea cucumber (Apostichopus japonicus) is a marine organism known for its medicinal properties. After conducting a bioinformatics analysis of the cDNA library of Apostichopus japonicus, we found and cloned a cDNA sequence encoding histidine-rich peptides, and the recombinant peptide was named rAj-HRP. Human histidine-rich peptides are known for their anti-cancer properties, raising questions as to whether rAj-HRP might exhibit similar effects. To investigate whether rAj-HRP can inhibit colon cancer, we used human colon cancer HCT116 cells as a model and studied the tumor suppressive activity in vitro and in vivo. The results showed that rAj-HRP inhibited HCT116 cell proliferation, migration, and adhesion to extracellular matrix (ECM) proteins in vitro. It also disrupted the cytoskeleton and induced apoptosis in these cells. In vivo, rAj-HRP significantly inhibited the growth of HCT116 tumors in BALB/c mice, reducing tumor volume and weight without affecting the body weight of the tumor-bearing mice. Western blot analysis showed that rAj-HRP inhibited HCT116 cell proliferation and induced apoptosis by upregulating BAX and promoting PARP zymogen degradation. Additionally, rAj-HRP inhibited HCT116 cell adhesion and migration by reducing MMP2 levels. Further research showed that rAj-HRP downregulated EGFR expression in HCT116 cells and inhibited key downstream molecules, including AKT, P-AKT, PLCγ, P38 MAPK, and c-Jun. In conclusion, rAj-HRP exhibits significant inhibitory effects on HCT116 cells in both in vitro and in vivo, primarily through the EGFR and apoptosis pathways. These findings suggest that rAj-HRP has the potential as a novel targeted therapy for colon cancer.

Broussoflavonol F exhibited anti-proliferative and anti-angiogenesis effects in colon cancer via modulation of the HER2-RAS-MEK-ERK pathway

BackgroundA prenylated flavonoid, broussoflavonol F (BFF), was isolated from Macaranga genus with cytotoxicities against various cancer cells, though its underlying mechanisms have not been fully elucidated. HypothesisThis study aimed to investigate the anti-tumor and anti-angiogenesis activities of BFF and its underlying mechanisms in colon cancer. MethodIn the in vitro study, the cytotoxic effects of BFF in human colon cancer HCT-116 and LoVo cells were examined using MTT assay, BrdU assay and colony formation assay. The anti-proliferative effects of BFF in these cells were assessed via cell apoptosis and cell cycle analysis using flow cytometry. The anti-angiogenesis effects of BFF in human endothelial HEMC-1 cells were also detected using scratch wound healing assay and tube formation assay. While the in vivo effects of BFF in colon cancer were further examined in zebrafish embryos and HCT116 tumor-bearing mice. The underlying mechanisms of BFF were predicted using network pharmacology analysis, and Western blotting was performed to validate both in vitro and in vivo results. ResultsBFF exhibited cytotoxicities on 5 colon cancer cell lines, as well as anti-proliferative activities via inducing apoptosis and cell cycle arrest at the G0/G1 phase in HCT116 and LoVo cells. BFF at 1.25-5 µM also suppressed cell proliferation in these two colon cancer cell lines by downregulating HER2, RAS, p-BRAF, p-MEK and p-Erk protein expressions. In addition, BFF at 2.5-5 µM could significantly decrease the length of subintestinal vessels of zebrafish embryos through decreasing mRNA expressions of NRP1a, PDGFba, PDGFRb, KDR, FLT1 and VEGRaa. Besides, BFF exhibited anti-angiogenesis activity via inhibiting cell proliferation, motility and tube formation in HMEC-1 cells. Furthermore, intraperitoneal administration of BFF (10 mg/kg) suppressed tumor growth and decreased the expression of tumor proliferation marker Ki-67 and angiogenesis marker CD31 in the tumor tissues in HCT116 tumor-bearing mice. BFF treatment could also significantly decrease expressions of RAS, p-BRAF, p-MEK and p-Erk in the tumor section, which are consistent with the in vitro results. ConclusionsThis study revealed the anti-tumor and anti-angiogenesis effects of BFF in colon cancer. This is the first report of the in vitro and in vivo anti-proliferative activity of BFF in colon cancer through regulating the HER2-RAS-MEK-ERK pathway. These findings further support the research development of BFF as an anti-cancer agent in colon cancer.

The m6A methyltransferase METTL3 modifies Kcnk6 promoting on inflammation associated carcinogenesis is essential for colon homeostasis and defense system through histone lactylation dependent YTHDF2 binding

Inflammation induces tumor formation and plays a crucial role in tumor progression and prognosis. KCNK6, by regulating K(+) efflux to reduce NLRP3 Inflammasome-induced lung injury, relaxes the aorta. This study aims to elucidate the effects and biological mechanism of KCNK6 in inflammation-associated carcinogenesis, which may be essential for colon homeostasis and the defense system. To induce colitis, mice were given 3.0% Dextran Sodium Sulfate (DSS) in their drinking water for 7 days. The Azoxymethane (AOM) +DSS method was used to induce colon cancer in the mice model. Bone marrow-derived macrophages (BMDM) from Kcnk6-/- mice, AW264.7 cells, and human colon cancer HCT116 and Caco2 cells were used as in vitro models. The loss of Kcnk6 prevented spontaneous colitis and restored mucosal integrity and homeostatic molecules. Additionally, the loss of Kcnk6 reduced the severity of AOM/DSS-induced carcinogenesis. Kcnk6 promoted cell viability and proliferation in HCT-116 or Caco-2 cells. The loss of Kcnk6 inhibited the levels of inflammatory factors in BMDM cells. Kcnk6 accelerated potassium channel activity, inducing NLRP3 inflammasome activation. METTL3-mediated m6A modification increased Kcnk6 stability in a YTHDF2-dependent manner. Histone lactylation activated the transcription of YTHDF2/Kcnk6. Our study revealed the important role of Kcnk6 in inflammation-associated carcinogenesis progression. The m6A methyltransferase METTL3 and histone lactylation increased Kcnk6 stability in a YTHDF2-dependent manner, providing a potential strategy for inflammation-associated carcinogenesis or colorectal cancer therapy.

Enhancement of Cinnamomum camphora magnetic nanoparticle bioactivities via carboxymethyl cellulose immobilization for potential therapeutic applications in cancer treatment

A promising method for cancer therapy is the coating of magnetic nanoparticles with carboxy methylcellulose. In a research project, hydroalcoholic extract of Cinnamomum camphora leaves was used to demonstrate the production of magnetic nanoparticles (MNPs); MNPs were coated with carboxymethyl cellulose to form carboxymethyl cellulose-coated magnetic nanoparticles (CMNPs)were formed. Preliminary phytochemical screening of C. camphora confirmed the presence of flavonoids, carbohydrates, phenolic compounds, and proteins. Phenolics 280.59 (mg/g), flavonoids 15.46 (mg/g), proteins 1.9 (mg/mL) and total carbohydrates 293.80 (mg/g) were all quantified. To confirm the formation of MNPs and CMNPs, UV–visible (UV–vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) were used. Peaks were observed at 232 nm and 240 nm, respectively. The largest absorption peaks were observed in MNPs and CMNPs, respectively. The particles were spherical in shape and less than 10 (nm) in diameter. The potential scavenging activity of biosynthesized MNPs and CMNPs was evaluated by the ABTS and DPPH assays, and the inhibition values IC50 were 141.3 ± 3.0 and 61.67 ± 2.5 (µg/mL) for ABTS and 176.1 ± 4.0 and 70.92 ± 3.0 (µg/mL) for DPPH, respectively (p ≤ 0.05). Furthermore, the cytotoxicity test results showed that the HCT-116 human colon cancer cell line had the lowest IC50 value of 20 (µg/mL) for CMNP, followed by the HepG2 hepatocellular carcinoma cell line with an IC50 value of 33 (µg/mL) for CMNP, indicating that the cytotoxic effect on colon cancer cells is stronger than on liver cancer cells. Molecular docking studies have revealed that CMNPs target and bind to apoptotic protein, enhancing their bioactivity and cytotoxic effects on cancer cells. Furthermore, our findings suggest that the induction of apoptosis may be responsible for the anticancer effects of CMNPs.Graphical abstract

Anti-Growth and Anti-Metastatic Potential of Raw and Thermally Treated Eragrostis tef Extract in Human Cancer Cells.

Teff (Eragrostis tef), a gluten-free cereal crop cultivated originally in Northeast Africa, is increasingly utilized due to its nutritional and health benefits. The aim of the present study was to investigate the effects of ethanol extract obtained from raw and thermally treated teff, referred to as RTE and TTE, respectively, on uncontrolled growth and activated metastasis using human cancer cell lines. Both RTE and TTE contained flavones, such as orientin (luteolin 8-C-glucoside) and vitexin (apigenin 8-C-glucoside), and phenolic acids, such as protocatechuic acid and p-coumaric acid. TTE showed higher total phenol, protocatechuic acid, and p-coumaric acid contents, but lower orientin content compared to RTE. RTE and TTE significantly suppressed cell growth of H1299 human lung cancer cells, with TTE exhibiting more pronounced effects than RTE, while both extracts had only minimal effects on the growth of non-malignant human umbilical vein endothelial cells. The growth-inhibitory activities of RTE and TTE in H1299 cells were associated with apoptosis induction and cell cycle arrest at the G2/M phase. TTE produced an additional effect on inducing cell cycle arrest at the S phase in H1299 cells, potentially contributing to its stronger growth-inhibitory effects. Moreover, both RTE and TTE effectively inhibited key events in metastasis, such as invasion, migration, and adhesion, in H1299 cells under non-cytotoxic conditions, with TTE showing stronger effects. In HCT116 human colon cancer cells, a similar pattern of inhibition was demonstrated against the metastatic events, accompanied by reduced levels of matrix metalloproteinase-2 and -9. Our results indicate that teff extracts exhibit in vitro anti-growth and anti-metastatic activities, which are enhanced by thermal treatment of teff.

Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells.

Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase- 3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways, respectively. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.

Design and Synthesis of Thiourea-Conjugating Organic Arsenic D-Glucose with Anticancer Activities.

Organic arsenic compounds such as p-aminophenylarsine oxide (p-APAO) are easier for structural optimization to improve drug-like properties such as pharmacokinetic properties, therapeutic efficacy, and target selectivity. In order to strengthen the selectivity of 4-(1,3,2-dithiarsinan-2-yl) aniline 7 to tumor cell, a thiourea moiety was used to strengthen the anticancer activity. To avoid forming a mixture of α/β anomers, the strategy of 2-acetyl's neighboring group participation was used to lock the configuration of 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate from 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide. 1-(4-(1,3,2-dithiarsinan-2-yl) aniline)-2-N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranos-1-yl)-thiourea 2 can increase the selectivity of human colon cancer cells HCT-116 (0.82 ± 0.06 μM vs. 1.82 ± 0.07 μM) to human embryonic kidney 293T cells (1.38 ± 0.01 μM vs. 1.22 ± 0.06 μM) from 0.67 to 1.68, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.

Cytotoxicity of alkaloids isolated from Peganum harmala seeds on HCT116 human colon cancer cells.

The present study aimed to elucidate the potential anticancer activity and mechanism of P. harmala's alkaloid extract, harmine (HAR), and harmaline (HAL) in HCT-116 colorectal cancer cells. P. harmala's alkaloid was extracted from harmala seeds. HCT-116 cells were treated with P. harmala's alkaloid extract, HAR and HAL. Cytotoxicity was determined by MTT assay, apoptotic activity detected via flow cytometry and acridine orange (AO)/ethidium bromide (EB) dual staining, and cell cycle distribution analyzed withflow cytometry. The mRNA expression of Bcl-2-associated X protein (Bax) and glycogen synthase kinase-3 beta (GSK3β) was measured by real-time PCR. Furthermore, the expression of Bax, Bcl-2, GSK3β and p53 proteins, were determined by western blotting. The findings indicated that, P. harmala's alkaloids extract, HAR and HAL were significantly cytotoxic toward HCT116 cells after 24 and 48h of treatment. We showed that P. harmala's alkaloid extract induce apoptosis and cell cycle arrest at G2 phase in the HCT116 cell line. Downregulation of GSK3β and Bcl-2 and upregulation of Bax and p53 were observed. The findings of this study indicate that the P. harmala's alkaloid extract has anticancer activity and may be further investigated to develop future anticancer chemotherapeutic agents.

Anti-Metastatic Effects of Standardized Polysaccharide Fraction from Diospyros kaki Leaves via GSK3β/β-Catenin and JNK Inactivation in Human Colon Cancer Cells.

A polysaccharide fraction from Diospyros kaki (PLE0) leaves was previously reported to possess immunostimulatory, anti-osteoporotic, and TGF-β1-induced epithelial-mesenchymal transition inhibitory activities. Although a few beneficial effects against colon cancer metastasis have been reported, we aimed to investigate the anti-metastatic activity of PLE0 and its underlying molecular mechanisms in HT-29 and HCT-116 human colon cancer cells. We conducted a wound-healing assay, invasion assay, qRT-PCR analysis, western blot analysis, gelatin zymography, luciferase assay, and small interfering RNA gene silencing in colon cancer cells. PLE0 concentration-dependently inhibited metastasis by suppressing cell migration and invasion. The suppression of N-cadherin and vimentin expression as well as upregulation of E-cadherin through the reduction of p-GSK3β and β-catenin levels resulted in the outcome of this effect. PLE0 also suppressed the expression and enzymatic activity of matrix metalloproteinases (MMP)-2 and MMP-9, while simultaneously increasing the protein and mRNA levels of the tissue inhibitor of metalloproteinases (TIMP-1). Furthermore, signaling data disclosed that PLE0 suppressed the transcriptional activity and phosphorylation of p65 (a subunit of NF-κB), as well as the phosphorylation of c-Jun and c-Fos (subunits of AP-1) pathway. PLE0 markedly suppressed JNK phosphorylation, and JNK knockdown significantly restored PLE0-regulated MMP-2/-9 and TIMP-1 expression. Collectively, our data indicate that PLE0 exerts an anti-metastatic effect in human colon cancer cells by inhibiting epithelial-mesenchymal transition and MMP-2/9 via downregulation of GSK3β/β-catenin and JNK signaling.

Identification and characterization of multidomain monothiol glutaredoxin 3 from diploblastic Hydra

Intracellular antioxidant glutaredoxin controls cell proliferation and survival. Based on the active site, structure, and conserved domain motifs, it is classified into two classes. Class I contains dithiol Grxs with two cysteines in the consensus active site sequence CXXC, while class II has monothiol Grxs with one cysteine residue in the active site. Monothiol Grxs can also have an additional N-terminal thioredoxin (Trx)-like domain. Previously, we reported the characterization of Grx1 from Hydra vulgaris (HvGrx1), which is a dithiol isoform. Here, we report the molecular cloning, expression, analysis, and characterization of another isoform of Grx, which is the multidomain monothiol glutaredoxin-3 from Hydra vulgaris (HvGrx3). It encodes a protein with 303 amino acids and is significantly larger and more divergent than HvGrx1. In-silico analysis revealed that Grx1 and Grx3 have 22.5% and 9.9% identical nucleotide and amino acid sequences, respectively. HvGrx3 has two glutaredoxin domains and a thioredoxin-like domain at its amino terminus, unlike HvGrx1, which has a single glutaredoxin domain. Like other monothiol glutaredoxins, HvGrx3 failed to reduce glutathione-hydroxyethyl disulfide. In the whole Hydra, HvGrx3 was found to be expressed all over the body column, and treatment with H2O2 led to a significant upregulation of HvGrx3. When transfected in HCT116 (human colon cancer cells) cells, HvGrx3 enhanced cell proliferation and migration, indicating that this isoform could be involved in these cellular functions. These transfected cells also tolerate oxidative stress better.

Pleonotoquinones, Cytotoxic Oxepinenaphthoquinones from Pleonotoma jasminifolia.

Two unusual naphthoquinones, named here as pleonotoquinones A (1) and B (2), were isolated along with two known anthraquinones (3 and 4) via chromatographic separations of an ethyl acetate extract of the roots of Pleonotoma jasminifolia. Compounds 1 and 2 are the first examples of quinones bearing a 2-methyloxepine moiety. The compounds were isolated with the aid of mass spectrometry and molecular networking, and their structures were resolved using 1D and 2D NMR and HRESIMS data. The isolated compounds were evaluated for their antiproliferative activity against human cancer cell lines, and compounds 1 and 2 displayed cytotoxicity against human colon cancer HCT116 cells (IC50 = 2.6 μM for compound 1 and IC50 = 4.3 μM for compound 2) and human liver cancer HepG2 cells (IC50 = 1.9 μM for compound 1 and IC50 = 6.4 μM for compound 2).

Genome-guided discovery of two undescribed 6,6-spiroketal polyketides and stereochemical correction of bafilomycins P and Q from the marine-derived Streptomyces sp. SCSIO 66814

Bafilomycins are macrocyclic polyketides with intriguing structures and therapeutic value. Genomic analysis of Streptomyces sp. SCSIO 66814 revealed a type I polyketide synthase biosynthetic gene cluster (BGC), namely blm, which encoded bafilomycins and featured rich post-modification genes. The One strain many compounds (OSMAC) strategy led to the discovery of six compounds related to the blm BGC from the strain, including two previously undescribed 6,6-spiroketal polyketides, streptospirodienoic acids D (1) and E (2), and four known bafilomycins, bafilomycins P (3), Q (4), D (5), and G (6). The structures of 1 and 2 were determined by extensive spectroscopic analysis, quantum calculation, and biosynthetic analysis. Additionally, the absolute configurations of the 6/5/5 tricyclic ring moiety containing six consecutive chiral carbons in the putative structures of 3 and 4 were corrected through NOE analysis, DP4+ calculation, and single-crystal X-ray diffraction data. Bioinformatic analysis uncovered a plausible biosynthetic pathway for compounds 1–6, indicating that both streptospirodienoic acids and bafilomycins were derived from the same blm BGC. Additionally, sequence analysis revealed that the KR domains of module 2 from blm BGC was B1-type, further supporting the configurations of 1–4. Notably, compounds 3 and 4 displayed significant cytotoxic activities against A-549 human non-small cell lung cancer cells and HCT-116 human colon cancer cells.

Colon cancer inhibitory properties of Caulerpa lentillifera polysaccharide and its molecular mechanisms based on three-dimensional cell culture model

Caulerpa lentillifera is rich in polysaccharides, and its polysaccharides show a significant effect in different biological activities including anti-cancer activity. As an edible algae-derived polysaccharide, exploring the role of colon cancer can better develop the application from a dietary therapy perspective. However, more in-depth studies of C. lentillifera polysaccharide on anti-colon cancer activity and mechanism are needed. In this study, we found that Caulerpa lentillifera polysaccharides (CLP) showed potential anti-colon cancer effect on human colon cancer cell HT29 in monolayer (IC50 = 1.954 mg/mL) and spheroid (IC50 = 0.402 mg/mL). Transcriptomics and metabolomics analyses revealed that CLP had an inhibitory effect on HT29 3D spheroid cells by activating aminoacyl-tRNA biosynthesis as well as arginine and proline metabolism pathways. Furthermore, the anti-colon cancer effects of CLP were confirmed through other human colon cancer cell HCT116 and LoVo in monolayer cells (IC50 = 1.890 mg/mL and 1.437 mg/mL, respectively) and 3D spheroid cells (IC50 = 0.344 mg/mL and 0.975 mg/mL, respectively), and three patient-derived organoids with IC50 values of 6.333–8.780 mg/mL. This study provided basic data for the potential application of CLP in adjuvant therapeutic food for colon cancer on multiple levels, while further investigation of detailed mechanism in vivo was still required.

R-phycoerythrin alginate/shellac beads by external gelation: Process optimization and the effects of gastrointestinal digestion for nutraceutical applications

This study aimed to evaluate an alginate/shellac mixture as wall material to develop an aqueous phycoerythrin (R-PE) encapsulation system by external gelation and to determine the effect of encapsulation on the biological properties of R-PE released during simulated gastrointestinal digestion. The Taguchi method was implemented to formulate beads with a high R-PE encapsulation efficiency (EE). The effect of the variables: feeding flow (90 and 20 mL h−1), distance (5 and 10 cms), and CaCl2 (5 and 15 g L−1) were optimized, and the bead size, sphericity factor (SF), and total R-PE content were characterized. Finally, the optimal alginate/shellac beads were subjected to in vitro dynamic gastrointestinal digestion. The results show that the beads formed under optimal conditions reached an EE value of 97.5 %. The CaCl2 concentration and feeding flow most affected the R-PE EE. The release of R-PE from alginate/shellac was affected at acid pH 1; however, the concentration was under 10 % of the total R-PE content showing promising targeting properties in terms of time and pH. The R-PE extracts and capsules were partially degraded in gastric and intestinal conditions; the mouth did not detect signals from the protein profile. The encapsulation of alginate/shellac led to higher R-PE contents at the end of digestion than non-encapsulated R-PE, suggesting a protective role. Significantly, from permeate streams, equivalent to the absorption of encapsulated R-PE, the bioavailability was 2.5 times higher than non-encapsulated R-PE. NMR results indicate the presence of R-PE and its methyl amino acids and oligosaccharides between 0.5 and 2.5 and 3.8–6.8 ppm, respectively. Cytotoxicity activity was observed for the R-PE extract on the HCT-116 human colon cancer cell line. The alginate/shellac as a wall material and ionic gelation technology used may determine the release of the R-PE pigment at an intestinal site and its antiproliferative effect on health.

Green synthesis of silver nanoparticles using Illicium verum extract: Optimization and characterization for biomedical applications

Abstract The synthesis of noble metal nanoparticles is currently experiencing substantial development and considerable attention. Plant extracts are commonly used for the biological synthesis of nanoparticles because they contain biologically active constituents. In our present study, silver nanoparticles (AgNPs) were synthesized using an aqueous Illicium verum (Star anise) extract to evaluate their antimicrobial, antioxidant, and cytotoxicity activities. For maximum yields of AgNPs, the extract (2.5 ml), silver ions (500 µM), and pH (8) were shown to be the ideal nanoparticle production parameters. The visual colour shifted from pale brown to dark brown when the ultraviolet-visible spectrophotometer was used to validate the synthesis of AgNPs. A transmission electron microscope was utilized to evaluate nanoparticles’ physical nature. The presence of silver metal with face-centred cubic symmetry was confirmed by X-ray diffraction analysis. Fourier-transform infrared spectroscopy was used to identify the functional groups in charge of reducing silver ions (Ag+) and the stability of AgNPs produced using the I. verum aqueous extract. The agar well diffusion method investigated the antibacterial activity of I. verum silver nanoparticles (Iv-AgNPs) against pathogenic bacteria and fungi. At higher doses (100 µg·mL−1), the highest zone of inhibition was observed, and spherical AgNPs demonstrated the antibacterial activity. The I. verum extract and Iv-AgNPs enhanced (70%) their free radical scavenging activity at 500 µg·mL−1 according to the 2,2-diphenyl-1-picrylhydrazyl assay. Moreover, the cytotoxicity of Iv-AgNPs against the HCT-116 human colon cancer cell line indicated cell inhibition in a dose-dependent manner. Ultimately, the findings of this study indicate that techniques used to produce AgNPs are environmental friendly, cost-effective, harmless, uncomplicated, and can effectively tackle a broad spectrum of medical and nutritional concerns.

Everolimus exerts anticancer effects through inhibiting the interaction of matrix metalloproteinase-7 with syndecan-2 in colon cancer cells.

Previous work showed that matrix metalloproteinase-7 (MMP-7) regulates colon cancer activities through an interaction with syndecan-2 (SDC-2) and SDC-2-derived peptide that disrupts this interaction and exhibits anticancer activity in colon cancer. Here, to identify potential anticancer agents, a library of 1,379 Food and Drug Administration (FDA)-approved drugs that interact with the MMP-7 prodomain were virtually screened by protein-ligand docking score analysis using the GalaxyDock3 program. Among five candidates selected based on their structures and total energy values for interacting with the MMP-7 prodomain, the known mechanistic target of rapamycin kinase (mTOR) inhibitor, everolimus, showed the highest binding affinity and the strongest ability to disrupt the interaction of the MMP-7 prodomain with the SDC-2 extracellular domain in vitro. Everolimus treatment of the HCT116 human colon cancer cell line did not affect the mRNA expression levels of MMP-7 and SDC-2 but reduced the adhesion of cells to MMP-7 prodomain-coated plates and the cell-surface localization of MMP-7. Thus, everolimus appears to inhibit the interaction between MMP-7 and SDC-2. Everolimus treatment of HCT116 cells also reduced their gelatin-degradation activity and anticancer activities, including colony formation. Interestingly, cells treated with sirolimus, another mTOR inhibitor, triggered less gelatin-degradation activity, suggesting that this inhibitory effect of everolimus was not due to inhibition of the mTOR pathway. Consistently, everolimus inhibited the colony-forming ability of mTOR-resistant HT29 cells. Together, these data suggest that, in addition to inhibiting mTOR signaling, everolimus exerts anticancer activity by interfering with the interaction of MMP-7 and SDC-2, and could be a useful therapeutic anticancer drug for colon cancer.NEW & NOTEWORTHY The utility of cancer therapeutics targeting the proteolytic activities of MMPs is limited because MMPs are widely distributed throughout the body and involved in many different aspects of cell functions. This work specifically targets the activation of MMP-7 through its interaction with syndecan-2. Notably, everolimus, a known mTOR inhibitor, blocked this interaction, demonstrating a novel role for everolimus in inhibiting mTOR signaling and impairing the interaction of MMP-7 with syndecan-2 in colon cancer.

A Facile Ugi/Ullmann Cascade Reaction to Access Fused Indazolo-Quinoxaline Derivatives with Potent Anticancer Activity.

A facile methodology for the construction of a complex heterocycle indazolo-fused quinoxalinone has been developed via an Ugi four-component reaction (U-4CR) followed by an intramolecular Ullmann reaction. The expeditious process features an operationally simple approach, time efficiency, and a broad substrate scope. Biological activity was evaluated and demonstrated that compound 6e inhibits human colon cancer cell HCT116 proliferation with an IC50 of 2.1 μM, suggesting potential applications for developing a drug lead in medicinal chemistry.

Synthesis, molecular docking study, and biological evaluation and of new thiadiazole and thiazole derivatives incorporating isoindoline-1,3-dione moiety as anticancer and antimicrobial agents

To highlight the importance of thiazole and thiadiazole derivatives in the progression of cancer and microbial treatments and to aid in drug design, we have synthesized a new series of 1,3,4-thiadiazole and 1,3-thiazole derivatives. These were created by a two-step reaction process: initially, 2-(4-(2-bromoacetyl)phenyl)isoindoline-1,3-dione was reacted with potassium thiocyanate, and then the resulting thiocyanate intermediate was coupled with aryl diazonium salts to produce iminothiadiazole derivatives. These derivatives served as crucial intermediates for further synthesizing a range of thiadiazole derivatives using different reagents. Additionally, treating 2-(4-(2-bromoacetyl) phenyl)isoindoline-1,3-dione with thiourea resulted in aminothiazole derivatives. These were further coupled with arenediazonium chloride to form 5-arylazoaminothiazole derivatives. All the synthesised compounds were characterised using IR, 1H NMR and 13C NMR spectrum data, as well as physical data. The assessment of the synthesized compounds on the HCT-116 human colon cancer cell line has yielded promising results. Specifically, compounds 3a, 3b, 4b, 5b, 6b, and 9b have shown noteworthy efficacy, suggesting their potential as anticancer agents. These compounds have demonstrated a greater potency compared to the standard drug, doxorubicin, highlighting their significance in cancer treatment research. The study assessed the activity of various newly synthesized compounds against diverse microorganisms, including bacteria and fungi. Notably, two of these compounds, specifically 4b and 7b, exhibited significant efficacy against both gram-positive and gram-negative bacteria, surpassing the performance of a standard antibacterial reference agent. Furthermore, molecular docking of new products revealed interactions with enzyme binding sites, aligning with in vitro findings. Additionally, in-silico studies confirmed their favourable oral bioavailability through ADME profiling.