Significant Anticancer Effects Research Articles

A New Benzo[6,7]oxepino[3,2-b] Pyridine Derivative Induces Apoptosis in Canine Mammary Cancer Cell Lines

CMC is the most frequently diagnosed cancer and one of the leading causes of death in non-spayed female dogs. Exploring novel therapeutic agents is necessary to increase the survival rate of dogs with CMC. MPOBA is a BZOP derivative that has a significant anticancer effect in a human cell line. The main goal of this study was to investigate the anticancer properties of MPOBA against two CMC cell lines (REM134 and CMGT071020) using a 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, a wound healing assay, a transwell migration assay, an Annexin V-FITC apoptosis assay with a flow cytometry analysis, a mRNA expression analysis using quantitative real-time PCR (qRT-PCR), and an immunohistochemistry (IHC). According to the accumulated studies, MPOBA caused significant concentration- and time-dependent reductions in cell proliferation and cell migration and induced apoptosis in both CMC cell lines. In gene expression analysis, nine canine genes, including TP53, BCL-2, BAX, epidermal growth factor receptor (EGFR), snail transcription factor (SNAIL), snail-related zinc-finger transcription factor (SLUG), TWIST, E-cadherin, and N-cadherin, were investigated. The mRNA expression results revealed that MPOBA induced upregulation of TP53 and overexpression of the pro-apoptotic gene BAX, together with an inhibition of BCL-2. Moreover, MPOBA also suppressed the mRNA expression levels of SNAIL, EGFR, and N-cadherin and induced upregulation of E-cadherin, crucial genes related to the epithelial-to-mesenchymal transition (EMT). However, there was no significant difference in the IHC results of the expression patterns of vimentin (VT) and cytokeratin (CK) between MPOBA-treated and control CMC cells. In conclusion, the results of the present study suggested that MPOBA exhibited significant anticancer activity by inducing apoptosis in both CMCs via upregulation of TP53 and BAX and downregulation of BCL-2 relative mRNA expression. MPOBA may prove to be a potential candidate drug to be further investigated as a therapeutic agent for CMC.

Theoretical studies and evaluation of anticancer properties of two cobalt(III) Schiff base complexes derived from 3,5-dichloro-2-hydroxybenzaldehyde and 1,2-phenylene diamine

This research aimed to synthesize a tetradentate symmetrical ligand, H2L, through the condensation reaction between 3,5-dichloro salicylaldehyde and 1,2-phenylenediamine. The produced ligand contains [N2O2] donor atoms and forms two new Co(III) Schiff base complexes, namely [CoIII(L)(1-MeIm)2]ClO4 (1) and [CoIII(L)(mrpln)2]ClO4 (2). Then, the structural characterization of these compounds was further examined by experimental techniques such as single x-ray diffraction, CHNS analysis, FT-IR spectroscopy, UV–Vis spectroscopy, and theoretical quantum chemical calculations. Furthermore, the structure's HOMO-LUMO energy gap and molecular electrostatic potential (MEP) were measured using the B3LYP/6–311 G method and compared to experimental data. Hirshfeld surface analysis was employed to investigate intermolecular interactions inside the crystal structures. Subsequently, an investigation was conducted to examine the biological characteristics of the ligand (H2L) and its complexes about SW-480 cancer cells, revealing significant anti-cancer effects. Molecular docking assessments were performed on both complexes to determine their propensity for binding the protein B-cell lymphorna (BCL-2, PDB ID: 4LXD).

Genoprotective role of pembrolizumab liposome in isolated lymphocytes from head and neck squamous cell carcinoma patients compared to those from healthy individuals in vitro

Pembrolizumab has shown significant anticancer effects against various human cancers. The present study investigated the effects of pembrolizumab liposome and nano (naked) forms in treated lymphocytes from head and neck squamous cell carcinoma (HNSCC) patients compared to healthy individuals. The level of oxidative DNA damage induced by hydrogen peroxide (H2O2) was also investigated. A concentration of 10 µg/ml of pembrolizumab liposome was used to treat the lymphocytes in the Comet and micronucleus assays based on the preliminary dosage optimization tests. To determine the cellular pathways involved in the protective role of pembrolizumab against H2O2, several proteins involved in apoptosis (P53, P21 and Bcl-2) were assessed. Pembrolizumab significantly reduced DNA damage and decreased the number of micronuclei in lymphocytes from HNSCC patients (p < 0.01) compared with healthy individuals. The 10 µg/ml of pembrolizumab liposome significantly reduced the oxidative stress induced by H2O2 and was effective in healthy and HNSCC groups using the Comet and micronucleus assays (p < 0.001). To our knowledge, this is the first report of pembrolizumab in liposome and naked forms exhibiting a protective effect on DNA damage in the treatment of HNSCC patients.

Novel sulfonamides unveiled as potent anti-lung cancer agents via tumor pyruvate kinase M2 activation.

This rational pursuit led to the identification of a novel sulfonamide derivative as a potent anti-lung cancer (LC) compound. Considering these results, we synthesized 38 novel sulfonamide derivatives with diverse skeletal structures. In vitro cytotoxicity assays revealed a potent and selective antiproliferative effect against A549 cells after evaluating a panel of cancer cell lines. Compound 9b has emerged as a potent activator of tumor pyruvate kinase M2 (PKM2), a protein known to play a critical role in LC. Apoptosis assays and cell cycle analysis demonstrated early apoptosis and G2 phase arrest. In silico studies demonstrated interactions between compound 9b and the activator binding site of PKM2. Surface plasmon resonance (SPR) experiments strongly indicated that 9b has a high affinity (K d of 1.378 nM) for PKM2. Furthermore, the increase in reactive oxygen species and decrease in lactate concentration suggested that compound 9b has significant anticancer effects. Notably, the increase in particle size following treatment with 9b suggested the tetramerization of PKM2. This work provides insights that might advance efforts to develop effective non-platinum anticancer agents.

Synthesis of a celastrol derivative as a cancer stem cell inhibitor through regulation of the STAT3 pathway for treatment of ovarian cancer.

Accumulating evidence suggests that the root of drug chemoresistance in ovarian cancer is tightly associated with subpopulations of cancer stem cells (CSCs), whose activation is largely associated with signal transducer and activator of transcription 3 (STAT3) signaling. Recently, celastrol has shown a significant anti-cancer effect on ovarian cancer, but its clinical translation is very challenging due to its oral bioavailability and high organ toxicity. In this study, a celastrol derivative (Cel-N) was synthesized to augment the overall efficacy, and its underlying mechanisms were also explored. Different ovarian cancer cells, SKOV3 and A2780, were used to evaluate and compare the anticancer effects. Cel-N displayed potent activities against all the tested ovarian cancer cells, with the lowest IC50 value of 0.14-0.25 μM. Further studies showed that Cel-N effectively suppressed the colony formation and sphere formation ability, decreased the percentage of CD44+CD24- and ALDH+ cells, and induced ROS production. Furthermore, western blot analysis indicated that Cel-N significantly inhibited both Tyr705 and Ser727 phosphorylation and reduced the protein expression of STAT3. In addition, Cel-N could dramatically induce apoptosis and cell cycle arrest, and inhibit migration and invasion. Importantly, Cel-N showed a potent antitumor efficacy with no or limited systemic toxicity in mice xenograft models. The anticancer effect of Cel-N is stronger than celastrol. Cel-N attenuates cancer cell stemness, inhibits the STAT3 pathway, and exerts anti-ovarian cancer effects in cell and mouse models. Our data support that Cel-N is a potent drug candidate for ovarian cancer.

Feasibility of the inhibitor development for cancer: A systematic approach for drug design.

The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants. Stat3 can bind to specific DNA response elements and serves as a transcription factor to promote the translation of some invasion/migration-related target genes, considered as a potential anticancer target. Here, molecular docking and molecular dynamics (MD) simulation both were used to explore molecular recognition of quercetin with Stat3. The results show that quercetin impairs DNA transcription efficiency by hindering Stat3 dimerization, partially destroying DNA conformation. Specifically, when the ligand occupies the SH2 cavity of the enzyme, spatial rejection is not conductive to phosphokinase binding. It indirectly prevents the phosphorylation of Y705 and the formation of Stat3 dimer. When the inhibitor binds to the DT1005 position, it obviously shortens the distance between DNA and DBD, enhances their binding capacity, and thereby reduces the degree of freedom required for transcription. This work not only provides the binding modes between Stat3 and quercetin, but also contributes to the optimization and design of such anti-cancer inhibitors.

Anticancer approach by targeted activation of a global inhibitor of sialyltransferases with acrolein

Chemical regulation of glycan synthesis at the targeted cancer cell surface in mice leading to significant anticancer effects without side effects.

Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.

Aim: Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed. Methods & results: We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines. Specifically, compound 16b, featuring a 5-hydroxybenzothiophene hydrazide scaffold, emerged as a potent inhibitor, displaying low IC50 values against key kinases and demonstrating significant anti-cancer effects, particularly against U87MG glioblastoma cells. It induced G2/M cell cycle arrest, apoptosis and inhibited cell migration by modulating apoptotic markers. Conclusion: 16b represents a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core.

Sustainable synthesis of bakuchiol-mediated gold nanoparticles for drug delivery against bacterial strains and tumor microenvironments, and its in silico target proteins identification.

The sustained synthesis of gold nanoparticles (GNPs) has gained significant attention in biomedical applications. In this study, we explored the antibacterial and anticancer potential of bakuchiol-mediated gold nanoparticles (Bak-GNPs). Bakuchiol, a natural compound found in Psoralea corylifolia seeds, serves as both a reducing and stabilizing agent for green synthesis of GNPs. Our objectives include network analysis, molecular docking, synthesis of GNPs, characterization, and antipathogenic and anticancer efficacy of Bak-GNPs against lung and liver cancers. Protein-protein interaction networks were analyzed to identify effective protein targets for bakuchiol in lung and liver cancers. A molecular docking study was performed to validate the efficacy of the target protein against lung and liver cancer. Furthermore, Bak-GNPs were synthesized using bakuchiol and characterized by various techniques such as UV-visible spectroscopy, dynamic light scattering (DLS), zeta potential transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy, and their potential against pathogens and lung and liver cancers. GNAI3 emerged as the most promising target, with a binding energy of -7.5 kcal/mol compared to PTGER3's -6.9 kcal/mol, different characterization techniques revealed the successful synthesis of Bak-GNPs. Bak-GNPs exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, as confirmed by minimum inhibitory concentration (MIC) values. Bak-GNPs demonstrated significant anticancer effects on A549 (lung cancer) and HepG2 (liver cancer) cells, with IC50 values of 11.19 μg/mL and 6.6 μg/mL, respectively. Induction of apoptosis and inhibition of cell proliferation were observed in both the cell lines. The increased production of reactive oxygen species (ROS) contributes to its anticancer effects. This study highlights promising biomedical applications of bakuchiol-mediated GNPs. This green synthesis approach using bakuchiol provides a sustainable method for producing nanoparticles with enhanced biological activities. Further exploration of the pharmacological properties and mechanisms of Bak-GNPs is required to optimize their therapeutic efficacy for clinical use.

Dual-mRNA Delivery Using Tumor Cell Lysate-Based Multifunctional Nanoparticles as an Efficient Colon Cancer Immunogene Therapy.

Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments. Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates. The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models. Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.

An interpretable artificial intelligence framework for designing synthetic lethality-based anti-cancer combination therapies

IntroductionSynthetic lethality (SL) provides an opportunity to leverage different genetic interactions when designing synergistic combination therapies. To further explore SL-based combination therapies for cancer treatment, it is important to identify and mechanistically characterize more SL interactions. Artificial intelligence (AI) methods have recently been proposed for SL prediction, but the results of these models are often not interpretable such that deriving the underlying mechanism can be challenging. ObjectivesThis study aims to develop an interpretable AI framework for SL prediction and subsequently utilize it to design SL-based synergistic combination therapies. MethodsWe propose a knowledge and data dual-driven AI framework for SL prediction (KDDSL). Specifically, we use gene knowledge related to the SL mechanism to guide the construction of the model and develop a method to identify the most relevant gene knowledge for the predicted results. ResultsExperimental and literature-based validation confirmed a good balance between predictive and interpretable ability when using KDDSL. Moreover, we demonstrated that KDDSL could help to discover promising drug combinations and clarify associated biological processes, such as the combination of MDM2 and CDK9 inhibitors, which exhibited significant anti-cancer effects in vitro and in vivo. ConclusionThese data underscore the potential of KDDSL to guide SL-based combination therapy design. There is a need for biomedicine-focused AI strategies to combine rational biological knowledge with developed models.

Epigenetic Modulation Enhances the Therapeutic Potential of All-Trans Retinoic Acid in Acute Myeloid Leukemia

Epigenetic dysregulation has been strongly associated with the development and progression of acute myeloid leukemia (AML). While all-trans retinoic acid (ATRA), a derivative of vitamin A, has demonstrated significant anti-cancer effects in acute promyelocytic leukemia (APL-AML), its clinical efficacy in non-APL AMLs has been limited. This limited response can be attributed, in part, to the epigenetic silencing of genes targeted by or involved in the ATRA pathway, rendering them unresponsive to the drug. Consequently, our research aims to overcome the epigenetic barriers in AML by combining ATRA with small molecules that possess epigenetic modulating properties. To investigate the activation of the retinoic acid pathway in response to ATRA and a library of over 650 small molecules with epigenetic activity, we transduced HEK-293 cells with the p-GreenFire-RARE-Tk-Luc reporter construct. Through the screening process, we have identified 11 compounds that show promise as potential candidates for combination therapy with ATRA in non-APL AML. Notably, when combined with ATRA, two specific compounds, a dual PI3K HDAC inhibitor, and a pan-PKC inhibitor, demonstrated a significant 4-5 fold increase in RARE activity, indicating a synergistic effect. To determine the impact of selected compounds on the functional level, we evaluated the viability, differentiation, and phosphorylation status of ERK1/2, AKT1, MAPK9, p38, and MAPK9 in various cell lines, including HL-60, KG1a, BMNC, and primary MSC and AML cells. The dual PI3K HDAC inhibitor and a pan-PKC inhibitor were noncytotoxic to HL60, BMNC, and primary MSC. Interestingly, dual PI3K HDAC inhibitor with and without ATRA reduced the viability of KG1α by more than 95%. Moreover, dual PI3K HDAC inhibitor and a pan-PKC inhibitor, when combined with ATRA, lead to a 2-3 fold increase in the differentiation of HL60 cells and a 2-4 fold increase in the differentiation of AML cells ex vivo compared to ATRA in combination with the LSD1 inhibitor TCP (treatment control protocol) and untreated cells from AML subtypes M1, M2, and M4. PI3K HDAC inhibitor combined with ATRA significantly reduced p-MAPK and p-p38 levels while increasing the phosphorylation of p53 in HL-60 cells. Furthermore, RNA sequencing and chromatin profiling by Cleavage Under Targets and Tagmentation (CUT&amp;Tag) were performed to gain additional insights into the molecular mechanisms involved. Based on obtained results, the combination of ATRA with specific dual PI3K HDAC and pan-PKC inhibitors holds promise as a potential therapeutic approach for AML. Nevertheless, further investigations, including studies utilizing patient-derived xenograft models, are warranted to validate the efficacy and feasibility of this proposed treatment strategy.

Anticancer effects of pH- sensitive carvacrol zinc oxide quantum dots on DMBA induced mammary carcinoma in female sprague dawley rats

ObjectivesThe current research explores the anticancer effects of pH sensitive CVC-ZnO QDs (Carvacrol-loaded Zinc Oxide Quantum Dots) on DMBA induced mammary carcinoma in rats. MethodsFemale SD rats were used, and mammary cancer was induced by chemical carcinogen via subcutaneous injection near the mammary gland. Different concentrations of CVC-ZnO QDs were orally supplemented to evaluate the optimum dose. We assessed the growth rate, body weight changes, tumor volume, tumor incidence and tumor burden in both the inducer and treatment groups. We also evaluated the biochemical parameters (antioxidant status, lipid peroxidation, detoxification enzymes, and lipid profile) and histopathological changes in the kidney and mammary tissues. ResultsOur findings indicate that CVC-ZnO QDs treated rats significantly decreased the tumor weight, incidence, burden, lipid peroxidation levels, phase I detoxification enzyme activities and increased the body weight, phase II detoxification enzyme activities, and antioxidant status compared to the DMBA alone treated rats. CVC-ZnO QDs treatment also altered the lipid profile of plasma and mammary tissue. Furthermore, histopathological results confirmed that the CVC-ZnO QDs protect against DMBA-mediated damage to the mammary and kidney. ConclusionThe findings indicate that the CVC-ZnO QDs administered at 4 mg/kg b.w exhibited a significant anticancer effect against DMBA-induced mammary cancer.

Synergistic effects of CuO/TiO2 -chitosan-farnesol nanocomposites: Synthesis, characterization, antimicrobial, and anticancer activities on melanoma cells SK-MEL-3.

The current investigation focuses on synthesizing copper oxide (CuO)-titanium oxide (TiO2 )-chitosan-farnesol nanocomposites with potential antibacterial, antifungal, and anticancer properties against Melanoma cells (melanoma cells [SK-MEL-3]). The nanocomposites were synthesized using the standard acetic acid method and subsequently characterized using an X-ray diffractometer, scanning electron microscope, transmission electron microscopy, and Fourier transform infrared spectroscopy. The results from the antibacterial tests against Streptococcus pneumoniae and Stapylococcus aureus demonstrated significant antibacterial efficacy. Additionally, the antifungal studies using Candida albicans through the agar diffusion method displayed a considerable antifungal effect. For evaluating the anticancer activity, various assays such as MTT assay, acridine orange/ethidium bromide dual staining assay, reactive oxygen species (ROS) generation assay, and mitochondrial membrane potential (MMP) analysis were conducted on SK-MEL-3 cells. The nanocomposites exhibited the ability to induce ROS generation, decrease MMP levels, and trigger apoptosis in SK-MEL-3 cells. Collectively, the findings demonstrated a distinct pattern for the synthesized bimetallic nanocomposites. Furthermore, these nanocomposites also displayed significant (p < 0.05) antibacterial, antifungal, and anticancer effects when tested on the SK-MEL-3 cell line.

Bovine Serum Albumin Nanoparticles Enhanced the Intranasal Bioavailability of Silybin in Rats.

Silybin (SLB), an important flavonoid from silymarin, displays significant hepatoprotective, anticancer, antioxidant, and neuroprotective effects. However, its therapeutic efficacy is limited by its low solubility and bioavailability. To address these challenges, we engineered bovine serum albumin (BSA) nanoparticles (NP) loaded with SLB (BSA-NP/SLB) using the coacervation method. BSA-SLB NP exhibited a spherical shape, a mean size of 197 nm, a polydispersity index of 0.275, a zeta potential of -34 mV, and an entrapment efficiency of 67%. X-ray diffraction analysis indicated amorphization of SLB upon encapsulation. Formulation stability was upheld over 180 days. In vitro release assays demonstrated controlled diffusion-erosion release, with approximately 40% SLB released within 0.5 h and 100% over 12 h. Intranasal administration of BSA-NP/SLB in rats improved SLB bioavailability by fourfold compared to free SLB. These findings highlight the promising potential of intranasally administered BSA-NP/SLB as an alternative approach to enhance SLB bioavailability, paving the way for innovative therapeutic applications.

Antiproliferative and Cytotoxic Properties of Propynoyl Betulin Derivatives against Human Ovarian Cancer Cells: In Vitro Studies.

Due to the incidence of ovarian cancer (OC) and the limitations of available therapeutic strategies, it is necessary to search for novel therapeutic solutions. The aim of this study was to evaluate the cytotoxic effect of betulin 1 and its propynoyl derivatives 2-6 against ovarian cancer cells (SK-OV-3, OVCAR-3) and normal myofibroblasts (18Co). Paclitaxel was used as the reference compound. The propynoyl derivatives 2-6 exhibited stronger antiproliferative and cytotoxic activities compared to betulin 1. In both ovarian cancer cell lines, the most potent compound was 28-propynoylbetulin 2. In the case of compound 2, the calculated IC50 values were 0.2 µM for the SK-OV-3 cells and 0.19 µM for the OVCAR-3 cells. Under the same culture conditions, the calculated IC50 values for compound 6 were 0.26 µM and 0.59 µM, respectively. It was observed that cells treated with compounds 2 and 6 caused a decrease in the potential of the mitochondrial membrane and a significant change in cell morphology. Betulin 1, a diol from the group of pentacyclic triterpenes, has a confirmed wide spectrum of biological effects, including a significant anticancer effect. It is characterized by low bioavailability, which can be improved by introducing changes to its structure. The results showed that chemical modifications of betulin 1 only at position C-28 with the propynoyl group (compound 2) and additionally at position C-3 with the phosphate group (compound 3) or at C-29 with the phosphonate group (compound 6) allowed us to obtain compounds with greater cytotoxic activity than their parent compounds, which could be used to develop novel therapeutic systems effective in the treatment of ovarian cancer.

Sol-gel synthesis and cytotoxicity evaluation of selenium-doped cerium oxide nanoparticles for biomedical applications.

Over the past few years, ovarian cancer is the second most commonly diagnosed cancer among women. Despite the widespread knowledge of its prevalence, the curative measures and survival rates for ovarian cancer have not improved significantly, making it a challenging condition. Nanotechnology has become increasingly prominent in the field of cancer treatment. Previous studies showed both cerium oxide nanoparticles (CONPs) and selenium (Se) had anti-cancer. Therefore, doping selenium into CONPs may exhibit a more significant anti-cancer effect on ovarian cancer cells. Cerium nitrate hexahydrate, sodium selenite, and gelatin were employed for the production of CONPs and Se-doped CONPs. The EDX, XRD, and TEM/PSA imaging were employed to investigate the structural characteristics and morphology of the synthesized Se-doped CONPs. The reactive oxygen species (ROS) level and TNF, IL-6, and IL-1B gene expression were evaluated after inoculating A2780 human epithelial ovarian carcinoma (HEOC) with Se-doped CONP. Statistical analysis was conducted using ANOVA, followed by Bonferroni's t-test for multiple group comparisons. Se-doped CONPs had IC50 of 113 and 49 PPM after 24 and 48 h, respectively. In addition, Se-doped CONPs with concentrations of 50 and 100 PPM significantly reduced to ROS levels in the HEOC cell line. Also, 50 and 100 PPM Se-doped CONPs lead to significantly reduced TNF, IL-6, and IL-1B gene expression compared to the control group in the HEOC cell line. Our study showed the potential anti-cancer effects of Se-doped CONPs on ovarian cancer cell lines.

Recent Strategies for Cancer Therapy: Polymer Nanoparticles Carrying Medicinally Important Phytochemicals and Their Cellular Targets.

Cancer is a leading cause of death in the world today. In addition to the side effects of the chemotherapeutic drugs used to treat cancer, the development of resistance to the drugs renders the existing drugs ineffective. Therefore, there is an urgent need to develop novel anticancer agents. Medicinally important phytochemicals such as curcumin, naringenin, quercetin, epigallocatechin gallate, thymoquinone, kaempferol, resveratrol, genistein, and apigenin have some drawbacks, including low solubility in water, stability and bioavailability issues, despite having significant anticancer effects. Encapsulation of these natural compounds into polymer nanoparticles (NPs) is a novel technology that could overcome these constraints. In comparison to the free compounds, phytochemicals loaded into nanoparticles have greater activity and bioavailability against many cancer types. In this review, we describe the preparation and characterization of natural phytochemical-loaded polymer NP formulations with significant antioxidant and anti-inflammatory effects, their in vitro and in vivo anticancer activities, as well as their possible cellular targets.

Combined anticancer effects of neutron radiation and genistein on prostate cancer cells

Prostate cancer is the most frequent cancer in men and the second largest cause of cancer-related mortality after lung cancer. Today, studies on neutron radiation therapy show that this method alone is not able to prevent the progression of the disease in most patients with prostate cancer, so it is better to combine neutron radiation with an auxiliary antitumor such as genistein. We found that genistein has anticancer properties and few antioxidant capabilities and could cause the death of prostate cancer cells, mostly through triggering apoptosis. Here the purpose of this study was to evaluate the effect of very low dose rate neutron irradiation emitted from 241Am-Be neutron source as well as the effect of the combination of neutron irradiation and adding the optimal concentration of genistein (480 μM) on the attenuation of prostate cancer PC3 cells in 3D culture environment. MTT assay, Neutral red assay, NO assay, Catalase activity, Reduced glutathione (GSH), Cytochrome c releasing, and Comet assay were used to assess the effect and type of mortality caused by neutron radiation and also neutron and genistein combination in prostate cancer cells. The results of cytotoxicity test reveal that very low dose rate neutron radiation (0.6 mGy/h) with or without genistein at 5, 10, 15, and 20h reduced the survival of prostate cancer cells. Moreover, the rate of necrosis due to the neutron effect at different irradiation times enhanced with the increasing time. Despite significant anticancer effect of Genistein, it cannot be used simultaneously with neutron radiation for prostate cancer treatment.

Neo-intline: integrated pipeline enables neoantigen design through the in-silico presentation of T-cell epitope

Neoantigen vaccines are one of the most effective immunotherapies for personalized tumour treatment. The current immunogen design of neoantigen vaccines is usually based on whole-genome sequencing (WGS) and bioinformatics prediction that focuses on the prediction of binding affinity between peptide and MHC molecules, ignoring other peptide-presenting related steps. This may result in a gap between high prediction accuracy and relatively low clinical effectiveness. In this study, we designed an integrated in-silico pipeline, Neo-intline, which started from the SNPs and indels of the tumour samples to simulate the presentation process of peptides in-vivo through an integrated calculation model. Validation on the benchmark dataset of TESLA and clinically validated neoantigens illustrated that neo-intline could outperform current state-of-the-art tools on both sample level and melanoma level. Furthermore, by taking the mouse melanoma model as an example, we verified the effectiveness of 20 neoantigens, including 10 MHC-I and 10 MHC-II peptides. The in-vitro and in-vivo experiments showed that both peptides predicted by Neo-intline could recruit corresponding CD4+ T cells and CD8+ T cells to induce a T-cell-mediated cellular immune response. Moreover, although the therapeutic effect of neoantigen vaccines alone is not sufficient, combinations with other specific therapies, such as broad-spectrum immune-enhanced adjuvants of granulocyte-macrophage colony-stimulating factor (GM-CSF) and polyinosinic-polycytidylic acid (poly(I:C)), or immune checkpoint inhibitors, such as PD-1/PD-L1 antibodies, can illustrate significant anticancer effects on melanoma. Neo-intline can be used as a benchmark process for the design and screening of immunogenic targets for neoantigen vaccines.