Healthy Fibroblast Cells Research Articles

Bioinspired Synthesis of Gold Nanoparticles for Enhanced Anti-Cancer Activity and Cell Viability Studies

Gold nanoparticles, or AuNPs, have garnered significant attention in biomedical research, especially in cancer therapy, due to their unique physicochemical properties. This work discusses the bioinspired production of gold nanoparticles (AuNPs) using plant extracts as reducing and stabilizing agents. This research conducted the synthesis. Transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR) were used to analyze the synthesized nanoparticles. These approaches were used to characterize the nanoparticles’ dimensions, morphology, stability, and functional groups. At a wavelength of 532 nm, the nanoparticles, averaging 18 ± 3 nm in size, exhibited a pronounced surface plasmon resonance (SPR) peak, indicating the efficacy of the manufacturing method. Cell viability assessments performed using HeLa (a cervical cancer cell type), MCF-7 (a breast cancer cell model), and WI-38 (a healthy fibroblast cell model) demonstrated a concentration-dependent reduction in cancer cell viability, with little impact on healthy cells. At a concentration of 100 µg/mL of AuNPs, the viability of HeLa and MCF-7 cells decreased to 35.2% and 41.7%, respectively. The viability of WI-38 cells was maintained at 83.4%. The analysis of apoptosis revealed that the AuNPs induced apoptosis in cancer cells. The early and late apoptosis rates in HeLa cells were 35.4% and 45.8%, respectively, but in MCF-7 cells, they were 32.5% and 42.1%. The therapeutic efficacy of the nanoparticles was significantly enhanced by the bioactive compounds isolated from the plant. The eco-friendly synthesis method used in this study not only provides a sustainable means for nanoparticle production but also enhances the potential for their application in anti-cancer therapies. The therapeutic applications of these bioinspired AuNPs will be further explored via in vivo tests, which will be the emphasis of next research.

Determining Stable Structure and in Vitro Antiproliferative Properties of a Novel 3-(2-((4-Trifluoromethyl)phenyl)amino)thiazol-4-yl)-2H-chromen-2-one Molecule.

Since coumarin and thiazole derivatives are known to have antioxidant properties, a novel derivative was synthesized in this article. 3-(2-((4-(trifluoromethyl)phenyl)amino)thiazol-4-yl)-2H-chromen-2-one (ATC) was synthesized as a novel compound with high yield and characterized by Raman, FT-IR, 13 C-NMR, and 1 H-NMR spectroscopic procedures and DFT calculations. In this study, the potential in vitro antiproliferative properties of the ATC compound were evaluated on colorectal cancer (HT29) and melanoma (SK-MEL-30) cell lines. According to the results, the compound was found to be significantly active, approximately 2.6-fold, against melanoma cells compared to healthy fibroblast (L929) cells. Unlike melanoma cells, the compound did not have any adverse effects on colorectal cancer cells. Due to these findings, the compound can be harnessed as a promising antiproliferative drug candidate for preclinical studies against melanoma.

Investigation of iso-propylchaetominine anticancer activity on apoptosis, cell cycle and Wnt signaling pathway in different cancer models

Dysregulation of the Wnt signaling pathway contributes to the development of many cancer types. Natural compounds produced with biotechnological systems have been the focus of research for being a new drug candidate both with unlimited resources and cost-effective production.In this study, it was aimed to reveal the effects of isopropylchaetominine on cytotoxic, cytostatic, apoptotic and Wnt signaling pathways in brain, pancreatic and prostate cancer.The IC50 values of isopropylchaetominine in U-87 MG, PANC1, PC3 and LNCaP cells were calculated as 91.94 μM, 41.68 μM, 54.54 μM and 7.86 μM in 72nd h, respectively. The metabolite arrests the cell cycle in G0/G1 phase in each cancer cells. Iso-propylchaetominine induced a 4.3-fold and 1.9-fold increase in apoptosis in PC3 and PANC1 cells, respectively. The toxicity of isopropylchaetominine in healthy fibroblast cells was assessed using the annexin V method, and no significant apoptotic activity was observed between the groups treated with the active substance and untreated. In U-87 MG, PANC1, PC3, and LNCaP cells under treatment with isopropylchaetominin, the expression levels of DKK3, TLE1, AES, DKK1, FRZB, DAB2, AXIN1/2, PPARD, SFRP4, APC and SOX17 tumor suppressor genes increased significantly. Decreases in expression of Wnt1, Wnt2, Wnt3, Wnt4, Wnt5, Wnt6, Wnt10, Wnt11, FRZ2, FRZ3, FRZ7, TCF7L1, BCL9, PYGO, CCND2, c-MYC, WISP1 and CTNNB1 oncogenic genes were detected.All these result shows that isopropylchaetominine can present promising new treatment strategy in different cancer types.

Novel tetrahydronaphthalen-1-yl-phenethyl ureas: synthesis and dual antibacterial-anticancer activities

Cancer and antibiotic-resistant bacterial infections are significant global health challenges. The resistance developed in cancer treatments intensifies therapeutic difficulties. In addressing these challenges, this study synthesised a series of N,N′-dialkyl urea derivatives containing methoxy substituents on phenethylamines. Using isocyanate for the efficient synthesis yielded target products 14–18 in 73–76% returns. Subsequently, their antibacterial and anticancer potentials were assessed. Cytotoxicity tests on cancer cell lines, bacterial strains, and a healthy fibroblast line revealed promising outcomes. All derivatives demonstrated robust antibacterial activity, with MIC values ranging from 0.97 to 15.82 µM. Notably, compounds 14 and 16 were particularly effective against the HeLa cell line, while compounds 14, 15, and 17 showed significant activity against the SH-SY5Y cell line. Importantly, these compounds had reduced toxicity to healthy fibroblast cells than to cancer cells, suggesting their potential as dual-functioning agents targeting both cancer and bacterial infections.

Cytotoxic meroterpenoids from brown alga Stypopodium schimperi (Kützing) Verlaque & Boudouresque with comprehensive molecular docking & dynamics and ADME studies

In this study, five known meroterpenoids sargaol (1), flabellinone (2), stypodiol (3), atomarianone A (4), atomarianone B (5), and a known steroid fucosterol (6) were isolated from brown alga Stypopodium schimperi. Their structures were elucidated by 1D- and 2D NMR and mass spectroscopic analyses. Isolated compounds were tested against human healthy fibroblast cells (CCD-1079Sk), and two different types of human breast cancer cell lines (MDA-MB-231 and MCF-7). They were also investigated by molecular docking studies on estrogen receptor alpha (ERα), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), cyclin-dependent kinases 2, 4 and 6 (CDK2/4/6) proteins. Molecular dynamics simulations were carried out to determine their ligand-protein stability and binding affinity. The four isolates (1-3, 6) showed strong cytotoxic activity in vitro against both cancer cell lines, particularly the aggressive MDA-MB-231 cell line, which was verified by in silico screening. Fucosterol was found to be the most selective compound against cancer cell lines, particularly the aggressive MDA-MB-231 cell line with a selectivity index (SI>16). The ADME prediction was also carried out and all the isolate compounds showed drug likeness. As a result, stypodiol and fucosterol were found to be the most potent compounds against both cancer cell lines by in vitro and in silico studies.

A clinically relevant large-scale biomanufacturing workflow to produce natural killer cells and natural killer cell-derived extracellular vesicles for cancer immunotherapy.

Natural killer cell-derived extracellular vesicles (NK-EVs) have shown promising potential as biotherapeutics for cancer due to their unique attributes as cytotoxic nanovesicles against cancer cells and immune-modulatory activity towards immune cells. However, a biomanufacturing workflow is needed to produce clinical-grade NK-EVs for pre-clinical and clinical applications. This study established a novel biomanufacturing workflow using a closed-loop hollow-fibre bioreactor to continuously produce NK-EVs from the clinically relevant NK92-MI cell line under serum-free, Xeno-free and feeder-free conditions following GMP-compliant conditions. The NK92 cells grown in the bioreactor for three continuous production lots resulted in large quantities of both NK cell and NK-EV biotherapeutics at the end of each production lot (over 109 viable cells and 1013 EVs), while retaining their cytotoxic payload (granzyme B and perforin), pro-inflammatory cytokine (interferon-gamma) content and cytotoxicity against the human leukemic cell line K562 with limited off-target toxicity against healthy human fibroblast cells. This scalable biomanufacturing workflow has the potential to facilitate the clinical translation of adoptive NK cell-based and NK-EV-based immunotherapies for cancer with GMP considerations.

The relationship between the chemical components and skin-related enzyme inhibition, antioxidant activities and toxicity profile of Helichrysum armenium subsp. armenium

The aerial parts of Helichrysum armenium subsp. armenium were subjected to methanol, ethyl acetate and n-hexane extraction. The extracts were evaluated for their in vitro enzyme inhibitory activity [lipoxygenase (LOX), tyrosinase and elastase], antioxidant activity and toxicity (on fibroblast cells). All the extracts displayed a weak effect on LOX and elastase. The ethyl acetate extract showed the highest inhibition on tyrosinase enzyme with IC50 = 460 µg/mL, while kojic acid had IC50 = 30 µg/mL. The methanol and ethyl acetate extracts compared to the n-hexane extract exhibited stronger DPPH• and ABTS•+ scavenging activity, as well as iron(II)-chelating potential, and were shown to have rich phenolic and flavonoid contents. The methanol extract was toxic to healthy fibroblast cells at a higher concentration with IC50 > 500 µg/mL compared to the other extracts. Phytochemical analysis of the extracts was made quantitatively by LC–MS/MS. The major components identified in the methanol and the ethyl acetate extracts were astragalin, quinic acid, apigenin-7-glycoside, isoquercitrin, chlorogenic acid, naringenin, apigenin and luteolin-7-glucoside. The compounds detected in the n-hexane extract were much fewer. Based on these findings, H. armenium subsp. armenium can be considered to be a natural raw material with the potential to be used in the cosmetic industry.

Tarin-Loaded Nanoliposomes Activate Apoptosis and Autophagy and Inhibit the Migration of Human Mammary Adenocarcinoma Cells.

Tarin, a lectin purified from Colocasia esculenta, promotes in vitro and in vivo immunomodulatory effects allied to promising anticancer and antimetastatic effects against human adenocarcinoma mammary cells. This makes this 47 kDa-protein a natural candidate against human breast cancer, a leading cause of death among women. Tarin encapsulated in pegylated nanoliposomes displays increased effectiveness in controlling the proliferation of a mammary adenocarcinoma lineage comprising MDA-MB-231 cells. The mechanisms enrolled in anticancer and antimetastatic responses were investigated by treating MDA-MB-231 cells with nano-encapsulated tarin at 72 μg/mL for up to 48h through flow cytometry and transmission electron microscopy (TEM). The safety of nano-encapsulated tarin towards healthy tissue was also assessed by the resazurin viability assay, and the effect of nanoencapsulated tarin on cell migration was evaluated by scratch assays. Ultrastructural analyses of MDA-MB-231 cells exposed to nanoencapsulated tarin revealed the accumulation of autophagosomes and damaged organelles, compatible with autophagy-dependent cell death. On the other hand, the flow cytometry investigation detected the increased occurrence of acidic vacuolar organelles, a late autophagosome trait, along with the enhanced presence of apoptotic cells, activated caspase-3/7, and cell cycle arrest at G0/G1. No deleterious effects were observed in healthy fibroblast cells following tarin nanoencapsulated exposition, in contrast to reduced viability in cells exposed to free tarin. The migration of MDA-MB-231 cells was inhibited by nano-encapsulated tarin, with delayed movement by 24 h compared to free tarin. The nanoliposome formulation delivers tarin in a delayed and sustained manner, as evidenced by the belated and potent antitumoral and anti-migration effects on adenocarcinoma cells, with no toxicity to healthy cells. Although further investigations are required to fully understand antitumorigenic tarin mechanisms, the activation of both apoptotic and autophagic machineries along with the caspase-3/7 pathway, and cell cycle arrest may comprise a part of these mechanisms.

Design, syntheses, theoretical calculations, MM-GBSA, potential anti-cancer and enzyme activities of novel Schiff base compounds

In this study, new Schiff base compounds (SB-F-OH, SB-Cl-OH and SB-Br-OH) were derived from chalcone-derived amine compounds containing halogen groups and 4-hydroxybenzaldehyde. Also, their phthalonitrile compounds (SB-F-CN, SB-Cl-CN and SB-Br-CN) have been synthesized. The structures of these compounds were elucidated by NMR, FT-IR and Mass spectroscopic methods. The quantum chemical parameters were calculated at B3LYP/6–31++g(d,p), HF/6–31++g(d,p) and M062X/6–31++g(d,p) levels. As the biological application of the synthesized compounds, (i) their inhibition properties of the synthesized compounds on Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) metabolic enzymes were investigated, and their potential anticancer activities against neuroblastoma (NB; SH-SY5Y) and healthy fibroblast (NIH-3T3) cell lines were determined by in vitro assays. All compounds showed inhibition at nanomolar level with the Ki values in the range of 97.86 ± 30.51–516.82 ± 31.42 nM for AChE, 33.21 ± 4.45–78.50 ± 8.91 nM for BChE, respectively. It has been determined that all tested compounds have a remarkable cytotoxic effect against SH-SY5Y, and IC50 values were significantly lower than NIH-3T3 cells. The lowest IC50 value was observed in SB-Cl-OH (7.48 ± 0.86 µM) and SB-Cl-CN (7.31 ± 0.69 µM). The molecular docking of the molecules was also investigated using crystal structure of AChE enzyme protein (PDB ID: 4M0E), crystal structure of BChE protein (PDB ID: 6R6V) and SH-SY5Y cancer protein (PDB ID: 2F3F, 3PBL and 5WIV). The ADME properties of the compounds were investigated. MM/GBSA method is calculated binding free energy. Afterwards, ADME/T analysis was performed to examine the some properties of the molecules. Communicated by Ramaswamy H. Sarma

Synergistic effects of ozone with doxorubicin on the proliferation, apoptosis and metastatic profile of luminal-B type human breast cancer cell line

ObjectiveLuminal-B type human breast cancer cell line (BT-474) to assess the synergistic effects of ozone applied after chemotherapeutic treatment with various dosages of doxorubicin, and compare the results with the effects on L929 fibroblast cell line. MethodsDoxorubicin (1–50 M) was added to each cell lines and left to sit for 24 h at 37 °C. Then, as combination groups, half of the groups were incubated with 30 g/mL ozone for 25 min. Tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), and matrix metalloproteinase-2 and − 9 (MMP-2 and MMP-9) levels were measured using the MTT test, flow cytometry, and immunocytochemistry, respectively. ResultsWhen compared to simply doxorubicin-applied cells without ozone treatment, each dose of doxorubicin + ozone treatment considerably boosted L929 viability but significantly decreased BT-474 viability. Additionally, the combination increased the apoptotic impact of doxorubicin on BT-474 but not L929 (P < 0.001). TGF-, MMP-2, and MMP-9 levels of L929 after combination were substantially higher than those of the other groups (P < 0.01). Doxorubicin's effect on BT-474's protein levels, which had significantly decreased in comparison to those of the other groups, was reversed by the combination treatment (P < 0.05). ConclusionDoxorubicin's anti-proliferative and apoptotic effects were enhanced by ozone treatment in BT-474 cells, but it also repaired and healed healthy fibroblast cells that had been harmed by the cytotoxicity of the chemotherapy drug. If doxorubicin and ozone treatment are coupled, BT-474 cells may develop resistance to it through expressions of TNF-α, TGF-β, MMP-2, and MMP-9.

Surface engineering of tin dioxide through chitosan: Band-gap tuning of spherical structure with oxygen vacancies for enhanced antibacterial therapeutic effects

Gram-negative (G-) bacteria-based infections have become a significant threat to global public health. These infections pose big challenges regarding treatment. The situation of emergency hospitalization due to bacterial infections requires alternative therapeutic strategies. To address these issues, the exploration of metal oxide hybrid NPs has significant attention for the development of new biocidal agents against bacterial infections. The antibacterial efficacy of SnO2 NPs depends on physio-chemical characteristics, including small particle size (decrease bacterial growth), the increasing band gap (increase redox capabilities), oxygen vacancies (ROS), leading to bacterial cell death. In the present work, the synthesized tin dioxide (SO) and chitosan-modified tin dioxide (CsSO) NPs exhibit the tetragonal rutile structure with spherical structure used to identify them by XRD and TEM analysis. The antibacterial activity of CsSO NPs was enhanced compared to SO NPs against (G-) bacterial strains. These small size (25 nm), bandgap (3.54 eV), and oxygen vacancies (505 & 537 nm) of CsSO NPs contribute to more ROS generation, leading to intracellular leakage and cell death. In vitro, the cytotoxicity of CsSO NPs showed lower toxicity to healthy fibroblast cells than that of SO NPs. These results confirmed that CsSO NPs are promising as bacterial agents for antibacterial therapy.

Synthesis, characterization and biological evaluation of three novel copper(II) clonixinate complexes with methylpyridines: Insights into structure, DNA and BSA binding properties and anticancer activity

Three novel mononuclear copper(II) complexes 1–3 with clonixinate anion (clon) derived from clonixin (Hclon) and α-, β-, or γ-methylpyridine (α-, β-, or γ-pic) were synthesised. The compounds were characterised by IR, UV–Vis and EPR spectroscopy and elemental analysis. The redox properties of the prepared complexes were studied by square wave voltammetry. The structure of the complexes [Cu(clon)2(α-pic)2] (1), [Cu(clon)2(β-pic)2] (2), [Cu(clon)2(γ-pic)2] (3) was determined by single-crystal X-ray analysis and the intermolecular interactions were studied by Hirshfeld surface analysis. The interaction of the studied complexes with calf thymus DNA was investigated by UV–Vis absorption titration and further investigation of the possible intercalative mechanism of action was carried out by fluorescence quenching studies with ethidium bromide-DNA adduct monitored via fluorescence emission spectroscopy. Interactions with bovine serum albumin were also evaluated by fluorescence emission spectroscopy. The cytotoxicity and selectivity of 1–3 were studied in vitro on a human breast cancer cell line (MCF-7), a lung cancer cell line (A549), a human glioblastoma cell line (U-118MG) and healthy human fetal lung fibroblast cells (MRC-5). All three complexes showed low to moderate ability to interact with calf thymus DNA, probably through partial intercalation, high and reversible binding to serum albumin and promising cytotoxic effects on the MCF-7 cancer cell line with reasonable selectivity for complexes 1 and 2. Finally, the mitochondrial respiratory capacity of MCF-7 tumour cells was also studied and showed a reduced activity after the addition of the studied complexes.

Chalcone-based dipolar cycloaddition of novel heteroaromatic compounds: Their anticancer examination

In this study, new chalcone-isoxazole-based hybrid derivatives (12, 13, 18, and 21) and chalcone-triazole hybrid molecules (26) were synthesized using the click chemistry approach. Among these hybrid molecules, 12, 13, 21, and 26 were obtained by combining azole pharmacophore groups such as thiazole, isoxazole, and 1,2,3-triazole. In addition, a new bioactive hybrid molecule (E)-3-(2-(1-((4- (3-(4-((3-(4-(benzyloxy) phenyl) isoxazol-5-yl) methoxy) phenyl)–3–oxoprop-1-en-1-yl) phenoxy)methyl)-1H-1,2,3-triazol-4-yl)thiazol-4-yl)-2H-chromen-2-one (18), which is a chalcone-isoxazole hybrid derivative with azido thiazole coumarin substitution, was synthesized. The chemical structures of synthesized compounds were characterized by spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and MALDI-TOF MS (18, 21, and 26). These novel chalcone-azole hybrids (12, 13, 18, 21, and 26) were investigated for their in-vitro anticancer activity against A549 cells, Capan-1 cell lines, and a healthy L929 fibroblast cell line, as well as the apoptotic and necrotic effects of these compounds on Capan-1 cell lines. Among the compounds tested, hybrid 18 showed the best activity in the A549 cell line, while it showed moderate activity in the Capan-1 cell line.

Determination of Constituents of Extract of Celtis tournefortii Lam. by LC-MS/MS, Investigation of Enzyme Inhibition, Antimicrobial and Anticancer Effects

Phytochemicals found in extracts obtained from plants are very important bioactive constituents. In this study, phytochemicals in extract content obtained from Celtis tournefortii .Lam. tree (CT) leaves were determined by a LC-MS method. The constituents with the major concentrations was found rutin (2479.89 µg ml-1), coumarin (1241.68 µg ml-1), biochanin A (1026.42 µg ml-1), shikimic acid (477.32 µg ml-1), chlorogenic acid (300.76 µg ml-1). The suppressive effects of CT extract on the growth of pathogenic strains were studied by microdilution method. It was observed that it caused suppression on the strains in the concentration range of 2.00-8.00 µg ml-1. The inhibition effects of the extract on acetyl cholinesterase and glutathione-S transferase enzyme activities were investigated, and 50% inhibitory values of enzyme activity were found to be 13.58 and 13.86, respectively. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method, the cell viability suppressive effects of CT leaf extract were studied in healthy skin fibroblast cells as well as ovarian, colon and brain cancer cells. It was observed that they created a 42%, 4.27%, and 14.29% suppression in cells, respectively.

Ultrasonic Transformation of Antibiotic Molecules into a Selective Chemotherapeutic Nanodrug.

Ultrasound-based engineering of carrier-free nanodrugs by supramolecular self-assembly has recently emerged as an innovative and environmentally friendly synthetic approach. By applying high-frequency sound waves (490 kHz) in aqueous solutions, the transformation of small chemotherapeutic and antibiotic drug molecules into carrier-free nanodrugs with anticancer and antimicrobial activities was recently achieved. The transformation of the antibiotic drug molecules, i.e., doxycycline, into stable nanodrugs (~130 nm) with selective anticancer activity was achieved without requiring organic solvents, chemical agents, or surfactants. The obtained nanodrug exhibited reactive oxygen species (ROS)-mediated cytotoxicity on human breast cancer (MDA-MB 231 cells) but a negligible antiproliferative effect on healthy fibroblast cells. Imaging by super-resolution microscopy (STORM) provided insights into the intracellular trafficking and endosomal escape of the nanodrugs. Overall, these findings suggest that small antibiotic drugs can be transformed into chemotherapeutic nanodrugs with high selectivity against cancer cells.

Physicochemical Characterization and Cytocompatibility Study of Lyophilized Cow Urine Powder

Cow urine is known for possessing therapeutic potency which is found to vary depending upon its physical forms such as fresh sterile urine, distillate, lyophilized powder, etc. In the current work, we demonstrate the physicochemical characteristics and cytocompatibility of lyophilized powder of cow urine obtained from Sahiwal and the pure Indian breed. We have used several analytical techniques, including Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) Spectroscopy, Differential Scanning Calorimetry (DSC), Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy – Energy Dispersive X-ray Spectroscopy (SEM-EDX) to examine the physical and chemical nature of cow urine powder obtained through lyophilization. SEM-EDX analysis showed clusters like morphology and revealed 25-30% of metal ions present in both samples. TGA analysis showed three steps of degradation sequentially most likely due to initial desorption of adsorbed water, urea degradation, and loss of glycoside moiety present in flavonoid. DSC data revealed the presence of both irregular (amorphous) and ordered molecular structures (crystalline) in the lyophilized powder of cow urine. &lt;sup&gt;1&lt;/sup&gt;H NMR spectra of all the prepared cow urine samples exhibited a similar trend and did not vary significantly and; confirming the presence of the same flavonoid/compounds in each sample. FTIR spectra of all the prepared cow urine samples exhibited a similar trend and did not vary significantly as observed through &lt;sup&gt;1&lt;/sup&gt;H NMR spectra. In addition, a cytocompatibility study and MTT assay using NIH-3T3 fibroblast cells revealed that lyophilized cow urine powders possessed no deleterious effects on healthy fibroblast cells. Thus, the outcomes provide a benchmark for further understanding of the lyophilized form of cow urine that could be potentially useful for analyzing its therapeutic value.

Synthesis of Brominated Lactones Related to Mycalin A: Selective Antiproliferative Activity on Metastatic Melanoma Cells and Inhibition of the Cell Migration.

Starting from D-xylonolactone and D-ribonolactone, several five-membered bromolactones, related to the C1-C5 portion of mycalin A lactone, have been synthesized. The bromination of D-ribonolactone with HBr/AcOH, without a subsequent transesterification step, has been studied for the first time, giving us most of the acetylated lactones investigated in the present study. For each compound, where possible, both the C-3 alcohol and the corresponding acetate were prepared. Evaluation of their anti-tumor activity showed that all the acetates possess a good cytotoxicity towards human melanoma (A375), human cervical adenocarcinoma (HeLa) and human metastatic melanoma (WM266) cancer cells, comparable or even higher than that displayed by the original mycalin A lactone. Lactone acetates derived from D-ribonolactone showed the higher selectivity of action, exhibiting a strong cytotoxicity on all the tested tumor cells but only a limited toxicity on healthy human dermal fibroblast (HDF) cells, used as a control. Wound healing assays showed that two of these substances inhibit the migration of the WM266 cells.

Combined Biological and Numerical Modeling Approach for Better Understanding of the Cancer Viability and Apoptosis.

Nowadays, biomedicine is a multidisciplinary science that requires a very broad approach to the study and analysis of various phenomena essential for a better understanding of human health. This study deals with the use of numerical simulations to better understand the processes of cancer viability and apoptosis in treatment with commercial chemotherapeutics. Starting from many experiments examining cell viability in real-time, determining the type of cell death and genetic factors that control these processes, a lot of numerical results were obtained. These in vitro test results were used to create a numerical model that gives us a new angle of observation of the proposed problem. Model systems of colon and breast cancer cell lines (HCT-116 and MDA-MB-231), as well as a healthy lung fibroblast cell line (MRC-5), were treated with commercial chemotherapeutics in this study. The results indicate a decrease in viability and the appearance of predominantly late apoptosis in the treatment, a strong correlation between parameters. A mathematical model was created and employed for a better understanding of investigated processes. Such an approach is capable of accurately simulating the behavior of cancer cells and reliably predicting the growth of these cells.

A sequential recovery extraction and biological activity of water-soluble sulfated polysaccharides from the polar red macroalgae Sarcopeltis skottsbergii

Algal biomass is comprised of a variety of biochemical components that make it a viable raw material for use in a variety of applications using a biorefining process. From the residual supernatant generated by high-pressure homogenization for the extraction of the R-phycoerythrin pigment, two soluble polysaccharides (neutral and acid fractions) were obtained. The composition of total carbon (C), hydrogen (H), nitrogen (N), and sulfur (S), gas chromatography–mass spectrometry (GC–MS), Fourier transform infrared (FTIR-ATR) spectroscopy, antioxidant capacity (ABTS) and antiproliferative in vitro and in vivo activities were evaluated. The two polysaccharides, which had a relatively high sulfate content, exhibited significant antioxidant activity in superoxide radical assay (ABTS) and high anti-proliferative effects on G-361, U-937, HCT-116 cancer cells. High selectivity index (>3) was observed for the acid extract on G-361 and U-937 cell lines, but a significant inhibitory effect on the growth of 1064sK healthy fibroblast cells was measured too. On the other hand, neutral fraction polysaccharides, with the lowest sulfate content and relatively lower radical scavenging rates, showed scarce antitumor activity, a high selectivity index on G-361 melanoma cancer cells and non-toxicity on healthy cells. This differential behavior was verified by testing toxicity and lethality of both polysaccharide extracts in and in vivo zebrafish embryo acute toxicity test. Following this method, the LC50 of the neutral fraction resulted much higher (1.477 mg mL−1, p ≈ 0.0000) than that of the acid fraction (0.080 mg mL−1, p ≈ 0.0000) at 72 h post-fertilization. During this period, a slight growth delay and/or rare teratogenic effects were also induced by these fractions at concentrations lower than their LC50. Overall, this study indicates that the antitumor, antioxidant and toxicity effects of polysaccharides may be related to the combined effects of sulfate and galactose contents from the residual supernatant bioprocess. The nutraceutical potential of the acid fractions is thus finally discussed.

SERS Detection of Breast Cancer‐Derived Exosomes Using a Nanostructured Pt‐Black Template

AbstractAt present, there are no cancer treatments that are both non‐invasive and highly accurate. New tests that can diagnose cancer at an early stage would help to facilitate such improved therapies, and many recent studies have focused on the development of liquid biopsy tests for this purpose. Exosomes are extracellular vesicles secreted by cells as a means of communication that can be simply collected from blood samples. Current studies have shown the potential of surface‐enhanced Raman spectroscopy (SERS) in differentiating cancerous cells from healthy cells. Herein, a bespoke platinum‐black (Pt‐black) SERS template is developed—via a cost‐effective fabrication method of electroplating—to detect malfunctioned (cancerous) exosomes. The results demonstrate that the Pt‐black SERS substrate exhibits stable and consistent spectra, which produces the high reproducibility required for a reliable diagnostic template. More importantly, using the Pt‐black SERS template allows for the differentiation of cancer‐derived exosomes (extracted from 4T1 cells—a triple‐negative breast cancer cell line) and exosomes from healthy fibroblast cells with an 83.3% sensitivity and a 95.8% specificity. This study establishes the potential of the Pt‐black template in detecting cancerous exosomes and lays a solid foundation for future studies in the clinical application of SERS in cancer diagnosis.