High Anticancer Potential Research Articles

Effect of luteolin on oxidative stress and inflammation in the human osteoblast cell line hFOB1.19 in an inflammatory microenvironment

BackgroundPeriapical lesions are characterized by periapical inflammation and damage to periapical tissues and eventually lead to bone resorption and even tooth loss. H2O2 is widely used in root canal therapy for patients with periapical inflammation. Luteolin possesses high anti-inflammatory, antioxidant, and anticancer potential. However, the underlying mechanism of the efficacy of H2O2 and luteolin on oxidative stress and inflammatory tissue has not been previously addressed. We aimed to investigate the anti-inflammatory and antioxidative effects of luteolin on H2O2-induced cellular oxidative inflammation.MethodsAfter human osteoblasts (hFOB1.19) were treated with lipopolysaccharide (LPS), luteolin, or H2O2, cell proliferation was analysed by using a cell counting kit-8 (CCK-8), cell apoptosis was measured by using flow cytometry, the production of reactive oxygen species (ROS) was evaluated by using an oxidation-sensitive probe DCFH-DA ROS assay kit, and the expression of genes and proteins was detected by using reverse transcription quantitative polymerase chain reaction (RT‒qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).ResultsWe demonstrated that inflammation is closely related to oxidative stress and that the oxidative stress level in the inflammatory environment is increased. Luteolin inhibited the H2O2-induced increase in the expression of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor α (TNF-α) and significantly repressed the H2O2-induced increase in ROS, as well as markedly strengthened superoxide dismutase (SOD) activity in hFOB1.19 cells. Moreover, we detected that luteolin may inhibit H2O2-induced hFOB1.19 cell injury by suppressing the NF-κB pathway.ConclusionWe elucidated that luteolin protected human osteoblasts (hFOB1.19) from H2O2-induced cell injury and inhibited the production of proinflammatory cytokines by suppressing the NF-κB signalling pathway. Our findings provide a potential drug for treating H2O2-induced periodontitis and cell injury.

Pre-mating exposure with hesperidin protects N-ethyl-N-nitrosourea-induced neurotoxicity and congenital abnormalities in next generation of mice as a model of glioma.

Chemical carcinogen-induced oxidative stress has a key role in cell signaling linked to the development of cancer. Oxidative stress leads to oxidative damage to cellular membranes, proteins, chromosomes and genetic material. It is thought that compounds like hesperidin with high antioxidant and anticancer potential can reduce development of cancer induced by chemical carcinogens via neutralizing their oxidative damages. We investigated protective effect of hesperidin against N-Ethyl-N-Nitrosourea (ENU)-induced neurotoxicity, congenital abnormalities and possible brain cancer after exposure of mice during pregnancy as model of glioma. The mice were divided to four groups; control (normal saline), ENU (40mg/kg daily for three consecutive days from the 17th to the 19th of pregnancy), hesperidin (pretreated with 25mg/kg for 30 consecutive days, before mating) + ENU and hesperidin alone. Developmental toxicity parameters (the number of pregnant mice, stillbirths, abortion, live and dead offspring), behavioral tests (novel object recognition, open field and elevated plus maze) were performed. Moreover, the activity of butrylcholinesterase and acetylcholinesterase enzymes, oxidative markers and histopathological abnormalities were detected in brain tissue. Our data showed that conversely, the pretreatment of hesperidin reduces various degrees of developmental toxicity, neurobehavioral dysfunction, neurotoxicity, oxidative stress and histopathological abnormalities induced by ENU as a neurotoxic and carcinogenic agent in the next generation. In conclusion, pre-mating exposure with hesperidin may open new avenues for prevention of primary brain cancer in next generation and could be valuable for enhancing the antioxidant defense and minimizing the developmental and neurotoxicity of DNA alkylating agents.

Ellagic Acid-Gold Nanoparticle Complex as Anticancer Agent in Triple-Negative Breast Cancer Cells

Triple-negative breast cancer (TNBC) is the most aggressive sub-type of breast cancer, mainly affecting premenopausal women. As it neither expresses hormone receptors nor overexpresses HER2 receptors, it is difficult to tackle this deadly disease effectively. It is a well-known fact that phytochemicals have remarkable therapeutic potential in the prevention and treatment of different disorders. One of the well-known phytochemicals, ellagic acid (EA) has shown better efficacy in the prevention and treatment of cancer in many preclinical and clinical settings. Therefore, in this study, ellagic acid gold nanoparticles (EA-AuNp) were synthesized and characterized to passively target TNBC cells through EPR effect. EA-AuNp were prepared using the direct reduction method and characterized by UV–Visible spectroscopy, DLS, XRD, EDX, TEM and FT-IR spectra. We found that it significantly suppressed the TNBC cell proliferation (IC[Formula: see text] 12 [Formula: see text]g/ml) compared to EA alone (IC[Formula: see text] 36 [Formula: see text]g/ml). Flow cytometry and live and dead assays revealed that EA-AuNp induced more cell death in TNBC cells compared to EA alone. Further, western blot analysis substantiated that EA-AuNp induced apoptosis by regulating the expression of Bcl-2, survivin, caspase 3 and caspase 9. In conclusion, EA-AuNp has high anti-cancer potential and additional preclinical and clinical studies are highly recommended.

In Vivo Studies and Flow Cytometric Investigation on Anticancer Potential of Selenium Nanoparticles Synthesized via Aqueous Extract of Clerodendron phlomidis

Nowadays, doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts, cereals, and mushrooms into their regular diet to maintain fitness and overall health. Selenium nanoparticles (SeNPs) exhibit strong chemopreventive capabilities. The anticipations for SeNPs with enhanced and tunable bioactive activities have led to a keen interest in phytofabrication. In this study, the aqueous extract of Clerodendron phlomidis plant leaves was utilized for the synthesis of SeNPs. In traditional Indian medicine, this plant extract is recognized as a significant anti-diabetic agent. The flavonoids tetrahydroxylflavone, 7-hydroxyflavanone, and 6,4’-dimethyl-7-acetoxy-scutellarein present in this plant leaf extract demonstrate excellent anticancer activity. These secondary metabolites exhibit the ability to reduce sodium selenite into SeNPs. At a concentration of 13 µg/mL, the synthesized SeNPs effectively inhibited the proliferation of the HepG2 cell line. The results suggest that the SeNPs possess promising anti-cancer potential against liver cancer and can be considered as a therapeutic agent for liver cancer treatment. Additionally, the cell cycle arrest induced by SeNPs was further confirmed by the fluorescence-activated cell sorting (FACS) method, indicating that SeNPs could efficiently differentiate cancer cells from normal cells. Notably, it showed a significant improvement in diethylnitrosamine (DEN)-induced Swiss Wistar rat groups. This scientific investigation highlights the high anti-cancer potential of SeNPs, positioning them as a promising therapeutic agent for liver cancer treatment.

Thymol and carvacrol derivatives as anticancer agents; synthesis, in vitro activity, and computational analysis of biological targets.

Various thymol and carvacrol derivatives have been synthesized to test the anticancer activity potential. Computational methods including network pharmacology and molecular docking approaches were utilized to identify and assess the potential biological targets relating to cancer. Amongst the synthesized derivatives the ethoxy-cyclohexyl analogues were consistently the most active against a panel of 10 different cancer cell lines covering a variety of origins. Biological target predictions revealed the AKT1 protein to be a core and central target of the most active compounds. Molecular docking identified a binding pocket within this protein in which the most active compounds bind. The incorporation of computational analysis methods and conventional structure-activity approaches identified analogues of thymol and carvacrol with the highest anticancer potential, and analyzed their possible biological targets in a comprehensive manner.

Combination of Indomethacin with Nanostructured Lipid Carriers for Effective Anticancer Therapy.

The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin. IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro. Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (-30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 μM. We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.

Unsymmetrical Pd(II) Pincer Complexes with Benzothiazole and Thiocarbamate Flanking Units: Expedient Solvent-Free Synthesis and Anticancer Potential.

Driven by the growing threat of cancer, many research efforts are directed at developing new chemotherapeutic agents, where the central role is played by transition metal complexes. The proper ligand design serves as a key factor to unlock the anticancer potential of a particular metal center. Following a recent trend, we have prepared unsymmetrical pincer ligands that combine benzothiazole and thiocarbamate donor groups. These compounds are shown to readily undergo direct cyclopalladation, affording the target S,C,N-type Pd(II) pincer complexes both in solution and in the absence of a solvent. The solid-phase strategy provided the complexes in an efficient and ecologically friendly manner. The resulting palladacycles are fully characterized using nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy and, in one case, by single-crystal X-ray diffraction (XRD). The solvent-free reactions are additionally analyzed by powder XRD. The pincer complexes exhibit remarkable cytotoxicity against several solid and blood cancer cell lines, including human colorectal carcinoma (HCT116), breast cancer (MCF7), prostate adenocarcinoma (PC3), chronic myelogenous leukemia (K562), multiple plasmacytoma (AMO1), and acute lymphoblastic leukemia (H9), with the dimethylamino-substituted derivative being particularly effective. The latter also induced an appreciable level of apoptosis in both parental and doxorubicin-resistant cells K562 and K562/iS9, vindicating the high anticancer potential of this type of palladacycles.

Synthesis and Evaluation of Anticancer Potential of Novel Benzopyran Derivatives Using MTT and in vitro Scratch Assays

Evidence over benzopyrans and azomethines high anticancer potential, intended present study to carry out the synthesis, characterization and anticancer activity of some new benzopyrans derivatives (NBD). Study involved synthesis of N'-(substituted benzylidene)-2-(2-oxo-2H-benzopyran-4-yloxy)acetohydrazide (2a-d) by hydrazination of substituted benzopyran ester (1). The structures of all the synthesized benzopyran derivatives (NBD 2a-d) were elucidated based on the IR, 1H NMR, 13C NMR and mass spectral data. The NBD 2a-d were further investigated for their cell viability (toxicity analysis) against HEK-293 and anticancer potential against MCF-7 cancer cell lines using MTT assay and in vitro scratch assay. Present study revealed that NBD 2a-d structures were in agreement with their IR, NMR and mass spectrometric characterization data. The cell viability study, MTT and in vitro scratch assay of NBD 2a-d, revealed compound 2d to exhibit highest anticancer activity and safety when compared with standard (irinotecan). Present study concludes NBD 2d to possess high anticancer potential and proven to be safer when compared with irinotecan, however further studies are needed to establish its clinical significance.

Synthesis and Structural Characterization of Novel Dimers of Dipyridothiazine as Promising Antiproliferative Agents.

Many new isomeric dipyridothiazine dimers have been presented as molecules with anticancer potential. These compounds were obtained in efficient syntheses of 1,6-, 1,8-, 2,7- and 3,6-diazaphenothiazines with selected alkylaromatic linkers. The structures of these compounds has been proven with two-dimensional spectroscopic techniques (COSY, NOESY, HSQC and HMBC) and high-resolution mass spectrometry (HRMS). In silico analyses of probable molecular targets were performed using the Way2Drug server. All new dimers were tested for anticancer activity against breast cancer line MCF7 and colon cancer line SW480. Cytotoxicity was assessed on normal L6 muscle cells. The tested dimers had high anticancer potential expressed as IC50 and the selectivity index SI. The most active derivative, 4c, showed an IC50 activity of less than 1 µM and an SI selectivity index higher than 100. Moreover, the compounds were characterized by low toxicity towards normal cells, simultaneously indicating a high cytostatic potential.

Intranasal delivery of poly (d-glucosamine) encrusted self-assembled lipidic nanovesicles to enhanced brain uptake of thymoquinone for management of Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is a grade IV primary malignant brain tumour, which is highly infiltrative and exhibits a poor prognosis which results in high mortality. Low solubility and stability are the major hurdles faced while developing drug delivery systems for the treatment of GBM. Therefore, this study focuses on the enhancement of brain uptake of thymoquinone (TH) by formulating poly (d-glucosamine) self-assembled lipidic nanovesicles for intranasal delivery using 3-level and 3-factor central composite design (CCD). The nanovesicles were formulated using thin film hydration technique and were spherical with the particle size of 129.13 ± 2.3 nm and 32.4 ± 2.4 mV of zeta potential. The formulation exhibited high entrapment and drug loading of TH i.e., 95.07 ± 0.8 % and 8.91 ± 0.2 % respectively. The nanovesicles attained a sustained release of TH of 89.62 ± 2.9 % in 48 h with improved drug permeation of 41.89 ± 1.61 % in 12 h from nasal mucosa with enhanced mucoadhesion of 72.98 ± 1.78 %. The in-vitro cellular studies indicated the high anticancer potential of TH by lowering the cell viability to 32.90 ± 0.91 % at 25 μg/mL (IC50;21.10 μg/mL) and high radical scavenging of 69.35 ± 1.91 % (IC50;18.10 μg/mL) and improved cellular uptake of 48.71 ± 0.10ng/100 cells. Greater bioavailability of TH in CNS (∼3 folds that of IV solution) was observed along with a high drug-targeting percentage (98.1 ± 3.90 %) and drug-targeting index (11.67 ± 1.87 %) post-intranasal administration of the formulation. Quantitative uptake of the formulation was estimated using fluorescence imaging, which showed higher uptake in tissues of the brain. The formulation was having very less hemolysis (<8 %). Hence the formulated carriers can be a promising tool for the treatment of GBM.

A Drug-Eluting Injectable NanoGel for Localized Delivery of Anticancer Drugs to Solid Tumors.

Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements.

Diffractaic acid exhibits thioredoxin reductase 1 inhibition in lung cancer A549 cells.

Lung cancer is the leading cause of cancer-related deaths all over the world. Therefore, it has gained importance in the development of new chemotherapeutic strategies to identify anticancer agents with low side effects, reliable, high anticancer potential, and specific to lung cancer cells. Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for lung cancer treatment because of its overexpression in tumor cells. Here, we aimed to examine the anticancer effect of diffractaic acid, a lichen secondary metabolite, in A549 cells by comparing it with the commercial chemotherapeutic drug carboplatin and also to investigate whether the anticancer effect of diffractaic acid occurs via TrxR1-targeting. The IC50 value of diffractaic acid on A549 cells was determined as 46.37 μg/mL at 48 h, and diffractaic acid had stronger cytotoxicity than carboplatin in A549 cells. qPCR results revealed that diffractaic acid promoted the intrinsic apoptotic pathway through the upregulation of the BAX/BCL2 ratio and P53 gene in A549 cells, which is consistent with the flow cytometry results. Furthermore, migration analysis results indicated that diffractaic acid impressively suppressed the migration of A549 cells. While the enzymatic activity of TrxR1 was inhibited by diffractaic acid in A549 cells, no changes were seen in the quantitative expression levels of gene and protein. These findings provide fundamental data on the anticancer effect of diffractaic acid on A549 cells targeting TrxR1 activity, suggesting that it could be considered a chemotherapeutic agent for lung cancer therapy.

Synthesis and Characterization of a New Alginate/Carrageenan Crosslinked Biopolymer and Study of the Antibacterial, Antioxidant, and Anticancer Performance of Its Mn(II), Fe(III), Ni(II), and Cu(II) Polymeric Complexes.

Natural polysaccharides are essential to a wide range of fields, including medicine, food, and cosmetics, for their various physiochemical and biological properties. However, they still have adverse effects limiting their further applications. Consequently, possible structural modifications should be carried out on the polysaccharides for their valorization. Recently, polysaccharides complexed with metal ions have been reported to enhance their bioactivities. In this paper, we synthesized a new crosslinked biopolymer based on sodium alginate (AG) and carrageenan (CAR) polysaccharides. The biopolymer was then exploited to form complexes with different metal salts including MnCl2·4H2O, FeCl3·6H2O, NiCl2·6H2O, and CuCl2·2H2O. The four polymeric complexes were characterized by Fourier-transform infrared spectroscopy (FT-IR), elemental analysis, ultraviolet-visible spectroscopy (UV-Vis), magnetic susceptibility, molar conductivity methods, and thermogravimetric analysis. The X-ray crystal structure of the Mn(II) complex is tetrahedral and belongs to the monoclinic crystal system with the space group P121/n1. The Fe(III) complex is octahedral and crystal data fit with the cubic crystal system with the space group Pm-3m. The Ni(II) complex is tetrahedral and crystal data correspond to the cubic crystal arrangement with the space group Pm-3m. The data estimated for the Cu(II) polymeric complex revealed that it is tetrahedral and belongs to the cubic system with the space group Fm-3m. The antibacterial study showed significant activity of all the complexes against both Gram-positive bacteria (Staphylococcus aureus and Micrococcus luteus) and Gram-negative (Escherichia coli and Salmonella typhimurium) pathogenic strains. Similarly, the various complexes revealed an antifungal activity against Candida albicans. The Cu(II) polymeric complex recorded a higher antimicrobial activity with an inhibitory zone reaching 4.5 cm against Staphylococcus aureus bacteria and the best antifungal effect of 4 cm. Furthermore, higher antioxidant values of the four complexes were obtained with DPPH scavenging activity varying from 73 to 94%. The two more biologically effective complexes were then selected for the viability cell assessments and in vitro anticancer assays. The polymeric complexes revealed excellent cytocompatibility with normal human breast epithelial cells (MCF10A) and a high anticancer potential with human breast cancer cells (MCF-7) which increase significantly in a dose-dependent manner.

Advanced polymeric metal/metal oxide bionanocomposite using seaweed Laurencia dendroidea extract for antiprotozoal, anticancer, and photocatalytic applications.

Biosynthesized nanoparticles are gaining popularity due to their distinctive biological applications as well as bioactive secondary metabolites from natural products that contribute in green synthesis. This study reports a facile, ecofriendly, reliable, and cost-effective synthesis of silver nanoparticles (AgNPs), copper oxide nanoparticles (CuONPs), and polymeric PVP-silver-copper oxide nanocomposite using ethanol extract of seaweed Laurencia dendroidea and were evaluated for antiprotozoal, anticancer and photocatalytic potential. The nanostructures of the AgNPs, CuONPs, and polymeric PVP-Ag-CuO nanocomposite were confirmed by different spectroscopic and microscopic procedures. The UV-vis spectrum displayed distinct absorption peaks at 440, 350, and 470 nm for AgNPs, CuONPs, and polymeric Ag-CuO nanocomposite, respectively. The average particles size of the formed AgNPs, CuONPs, and Ag-CuO nanocomposite was 25, 28, and 30 nm, respectively with zeta potential values -31.7 ± 0.6 mV, -17.6 ± 4.2 mV, and -22.9 ± 4.45 mV. The microscopic investigation of biosynthesized nanomaterials revealed a spherical morphological shape with average crystallite sizes of 17.56 nm (AgNPs), 18.21 nm (CuONPs), and 25.46 nm (PVP-Ag-CuO nanocomposite). The antiprotozoal potential of green synthesized nanomaterials was examined against Leishmania amazonensis and Trypanosoma cruzi parasites. The polymeric PVP-Ag-CuO nanocomposite exerted the highest antiprotozoal effect with IC50 values of 17.32 ± 1.5 and 17.48 ± 4.2 µM, in contrast to AgNPs and CuONPs. The anticancer potential of AgNPs, CuONPs, and polymeric PVP-Ag-CuO nanocomposite against HepG2 cancer cell lines revealed that all the nanomaterials were effective and the highest anticancer potential was displayed by PVP-Ag-CuO nanocomposite with IC50 values 91.34 µg mL-1 at 200 µg mL-1 concentration. Additionally, PVP-Ag-CuO nanocomposite showed strong photocatalytic effect. Overall, this study suggested that the biogenic synthesized nanomaterials AgNPs, CuONPs, and polymeric PVP-Ag-CuO nanocomposite using ethanol extract of seaweed L. dendroidea possesses promising antiprotozoal anticancer and photocatalytic effect and could be further exploited for the development of antiprotozoal and anticancer therapeutics agents.

The Investigation of the Chemical Composition and Applicability of Gold Nanoparticles Synthesized with Amygdalus communis (Almond) Leaf Aqueous Extract as Antimicrobial and Anticancer Agents

The current work's main objective was to determine the chemical composition of Amygdalus communis (AC) leaf extract and examine the antibacterial and cytotoxic properties of biosynthesized gold nanoparticles (AuNPs). The chemical composition of AC leaf extract was determined using LC-ESI/MS/MS to detect compounds that may be responsible for the reducing, stabilizing, and capping steps in the synthesis of nanoparticles and their biological activities. The AC-AuNPs were spherical, with a particle size lower than 100 nm and a face-centered cubic structure. The EDX spectrum confirmed the formation of AuNPs and a negative zeta potential value (-27.7 mV) suggested their physicochemical stability. The in vitro cytotoxic efficacy of the AC-AuNPs against colorectal adenocarcinoma (Caco-2), glioma (U118), and ovarian (Skov-3) cancer cell lines and human dermal fibroblasts (HDFs) was evaluated by MTT assay. CaCo-2 cell proliferation was effectively inhibited by the AC-AuNPs at concentrations between 25 and 100 g mL-1. The AC-AuNPs exerted preeminent antimicrobial activity against Bacillus subtilis with an MIC of 0.02 μg/mL, whilst good activity was shown against Staphylococcus aureus bacteria and Candida albicans yeast with an MIC of 0.12 μg/mL. Ultimately, the results support the high antibacterial and anticancer potential of biosynthesized AuNPs from AC leaf extract.

Biosynthesized Silver Nanoparticles Using Morus alba (White Mulberry) Leaf Extract as Potential Antibacterial and Anticancer Agents.

In this study, we report the green synthesis of silver nanoparticles (AgNPs) from Morus alba or white mulberry leaf extract (MLE) and assess their antibacterial and anticancer potential. The GC-MS analysis of MLE confirmed the existence of phenolic compounds, serving as reducing, capping, and stabilizing agents in the biosynthesis of AgNPs. The MLE-AgNPs were spherical, with an average particle size of 20-44.5 nm and a face-centered cubic structure. EDX spectra confirmed the formation of AgNPs, and a negative zeta potential value (-14.5 mV) suggested their physicochemical stability. Excellent antibacterial activity was demonstrated by MLE-AgNPs against Acinetobacter baumannii strains with a MIC of 2 μg/mL, while good activity was observed against other Gram-negative (Escherichia coli and Salmonella typhimurium) and Gram-positive (Bacillus subtilis and Staphylococcus aureus) bacteria with a MIC of 32 μg/mL. In vitro cytotoxic effects on MCF-7 (human breast cancer cells) and MCF-10A (normal human mammary epithelial cells) were investigated by the MTT assay. The half-maximal inhibitory concentrations (IC50) against MCF-7 cells were 18 and 33 μg/mL for MLE-AgNPs and MLE, respectively, with no effect on normal MCF-10A cells. Altogether, the results support the high antibacterial and anticancer potential of biosynthesized AgNPs by white mulberry leaf extract.

Co-Delivery System of Curcumin and Colchicine Using Functionalized Mesoporous Silica Nanoparticles Promotes Anticancer and Apoptosis Effects.

Many natural agents have a high anticancer potential, and their combination may be advantageous for improved anticancer effects. Such agents, however, often are not water soluble and do not efficiently target cancer cells, and the kinetics of their action is poorly controlled. One way to overcome these barriers is to combine natural agents with nanoparticles. Our aim in the current study was to fabricate an anticancer nanoformulation for co-delivery of two natural agents, curcumin (CR) and colchicine (CL), with a core-shell structure. Using cancer cell lines, we compared the anticancer efficacy between the combination and a nanoformulation with CL alone. For the single-drug nanoformulation, we used phosphonate groups to functionalize mesoporous silica nanoparticles (MSNs) and loaded the MSNs with CL. Additional loading of this nanoformulation with CR achieved the co-delivery format. To create the structure with a core shell, we selected a chitosan-cellulose mixture conjugated with targeting ligands of folic acid for the coating. For evaluating anticancer and apoptosis effects, we assessed changes in important genes and proteins in apoptosis (p53, caspase-3, Bax, Bcl-2) in several cell lines (MCF-7, breast adenocarcinoma; HCT-116, colon carcinoma; HOS, human osteosarcoma; and A-549, non-small cell lung cancer). Nanoformulations were successfully synthesized and contained 10.9 wt.% for the CL single-delivery version and 18.1 wt.% for the CL+CR co-delivery nanoformulation. Anticancer effects depended on treatment, cell line, and concentration. Co-delivery nanoformulations exerted anticancer effects that were significantly superior to those of single delivery or free CL or CR. Anticancer effects by cell line were in the order of HCT-116 &gt; A549 &gt; HOS &gt; MCF-7. The lowest IC50 value was obtained for the nanoformulation consisting of CL and CR coated with a polymeric shell conjugated with FA (equivalent to 4.1 ± 0.05 µg/mL). With dual delivery compared with the free agents, we detected strongly increased p53, caspase-3, and Bax expression, but inhibition of Bcl-2, suggesting promotion of apoptosis. Our findings, although preliminary, indicate that the proposed dual delivery nanoformulation consisting of nanocore: MSNs loaded with CL and CR and coated with a shell of chitosan-cellulose conjugated folic acid exerted strong anticancer and apoptotic effects with potent antitumor activity against HCT-116 colon cells. The effect bested CL alone. Evaluating and confirming the efficacy of co-delivery nanoformulations will require in vivo studies.

Antiproliferative and Antioxidant Activities of Chloroform Soluble and its Fractions Obtained from Methanolic Extract of Cocoa pod Husk

Cocoa pod husk (Theobroma cacao L.) is an emerging source of bioactive compounds, revealed to possess anti-cancer potential by several reports. Herein, we aimed to investigate the antiproliferative and antioxidant activities of chloroform soluble (TCC) along with its 11 fractions (TCC1-11) obtained following the methanolic maceration of cocoa pod husk. Firstly, air-dried simplicial powder of cocoa pod husk was macerated using methanol and subsequently partitioned using n-hexane, ethyl acetate, and acetone. The insoluble part was then hydrolyzed with HCl (6%) and followed by further separation using chloroform yielding TCC (0.712 g; 0.93% w/w). Fractionation was further carried out using n-hexane and ethyl acetate solvents with an elution gradient system. TCC was revealed to have cytotoxicity against A. salina with LC50 equals to 105.04 mg/L, and the LC50s of its fractions ranged from 1.42 to 10.67 mg/L. Based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of TCC, the IC50 was obtained as low as 4.56 mg/L. Relatively less potent antioxidant activities were shown by the TCC1-11, where the IC50s were ranged from 284.478 to 37.909 mg/L. The highest anticancer potential was TCC10 (LC50 = 1.42 mg/L). With such anti-cancer potential, more investigations on the TCC and its fraction are required to determine the phytocompound profiles as well as the anti-cancer mechanism.

Bioactive Potential: A Pharmacognostic Definition through the Screening of Four Hypericum Species from the Canary Islands

In this work, we propose a general methodology to assess the bioactive potential (BP) of extracts in the quest of vegetable-based drugs. To exemplify the method, we studied the anticancer potential (AP) of four endemic species of genus Hypericum (Hypericum canariense L, Hypericum glandulosum Aiton, Hypericum grandifolium Choisy and Hypericum reflexum L.f) from the Canary Islands. Microextracts were obtained from the aerial parts of these species and were tested against six human tumor cell lines, A549 (non-small-cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small-cell lung), T-47D (breast) and WiDr (colon). The methanol–water microextracts were evaluated further for cell migration, autophagy and cell death. The most promising bioactive polar microextracts were analyzed by UHPLC–DAD–MS. The extraction yield, the bioactivity evaluation and the chemical profiling by LC–MS suggested that H. grandifolium was the species with the highest AP. Label-free live-cell imaging studies on HeLa cells exposed to the methanol–water microextract of H. grandifolium enabled observing cell death and several apoptotic hallmarks. Overall, this study allows us to select Hypericum grandifolium Choisy as a source of new chemical entities with a potential interest for cancer treatment.

Self-assembling nanoparticles based on acetate derivatives of calix[4]resorcinol and octenidine dihydrochloride for tuning selectivity in cancer cells

The search for highly active and highly selective antitumor agents with minimal side effects remains an urgent task, since commercial anticancer drugs have a low selectivity index. Reducing the impact on normal tissues while maintaining a high anticancer potential should be a key parameter in the development of a dosage form. In recent years, a high anticancer activity of octenidine has been reported on various cell lines. However, being a cationic surfactant, octenidine has a high toxicity, which can be reduced by incorporating it into biocompatible nanoparticles. In this work, biomimetic vesicular systems based on amphiphilic calix[4]resorcinols functionalized along the upper rim with acetate groups and octenidine dihydrochloride were obtained. The morphology of the obtained aggregates was confirmed by transmission electron microscopy and dynamic light scattering data. Calixarene–octenidine nanoparticles showed high cytotoxic activity (IC50 =0.4 µM) toward the human duodenal adenocarcinoma HuTu 80 cell line, as well as high selectivity (Selectivity Index > 20), which makes it possible to consider calixarene–octenidine nanoparticles as promising drug candidates.