Antitumor Effects Research Articles

Unleashing the Power of Cold Atmospheric Plasma: Inducing Mitochondria Damage-Mediated Mitotic Catastrophe.

Despite the promise of cold atmospheric plasma (CAP) for cancer treatment, the challenges associated with the treatment of solid tumors and penetration depth limitations remain, restricting its clinical application. Here, biological evidence is provided that the killing effect of CAP treatment is confined to less than 500µm subcutaneously and the actual biological dose decreased gradually with depth for the first time, indicating that the limited penetration depth has become an urgent problem that demands immediate solutions. Significantly, it is showed that different from high-dose treatments, CAP decreased the doses to the low-dose range but still exhibited anti-tumor effects via mitotic catastrophe. Unlike radiotherapy or chemotherapy, low-dose CAP treatment induces mitochondrial structural damage and dysfunction, disrupts energy metabolism and redox balance, and results in mitotic catastrophe. Collectively, these findings suggest that better understanding and taking full advantage of the dose-response gradient effect of CAP is a potential strategy to prompt its clinical application beyond improving CAP penetration.

Anticancer Effect of Cycas media: Molecular Basis Through Modulation of PI3K/AKT/mTOR Signaling Pathway

Many researchers are focusing on screening the biological activities of plants owing to their safety and possible pharmacological actions. Consequently, we aimed to explore the antiproliferative and cytotoxic properties of Cycas media methanolic extract on HepG2 cell lines. Moreover, we also explore the antitumor action against the experimentally induced solid Ehrlich carcinoma (SEC) model and investigate the possible involved molecular mechanisms. Also, the antibacterial action of the extract was elucidated. Different concentrations of the extract were incubated with HepG2 to determine cytotoxicity, followed by cell cycle analysis. The in vivo experiment was accomplished by grouping the animals into four different groups (n = 10); normal control, SEC, C. media 100, and C. media 200. The extract was administered at 100 and 200 mg/kg. Tumor volume, tumor inhibition rate, toxicity profile, and antioxidant biomarkers were determined. Moreover, the PI3K/AKT/mTOR signaling pathway was investigated as a possible underlying antitumor mechanism. The tumor control group showed a remarkable upregulation for PI3K, p-AKT, and p-mTOR, along with downregulation for the antioxidant SOD and GPX4, as well as decreased levels of GSH and MDA. C. media extract reversed these parameters to a significant level and the higher dose showed a superior antitumor effect. C. media extract showed antiproliferative effects against HepG2 cells, along with a suppressive action on the PI3K/AKT/mTOR pathway and an antioxidant effect. Additionally, C. media had antibacterial consequences against S. aureus isolates with minimum inhibitory concentrations from 32 to 128 µg/mL. It also caused a noteworthy growth delay as well as a notable reduction in the membrane integrity of S. aureus isolates. These beneficial outcomes suggest C. media to have potential antitumor and antibacterial activities.

Investigating the Mechanisms of Anti-tumoral Effect of Combination Therapy of Calcitriol and Sodium Pentaborate Pentahydrate on HepG2 Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is one of the most common primary liver cancers worldwide and is often associated with poor prognosis due to drug resistance. Combination therapies demonstrate superior efficacy at lower drug dosages on cancer cells compared to single treatments, resulting in less drug resistance in the cells. This study investigates the synergistic anti-tumoral effects of calcitriol, the biologically active form of vitamin D, and sodium pentaborate pentahydrate (NaB) on HepG2 cells. We examined the cell viability of NaB, calcitriol, or the combination of NaB and calcitriol on HepG2 cells and healthy human hepatic stellate cells (HHSC) using MTS. Our findings showed that combination therapy with 3.3mM NaB and 1µM calcitriol has a synergistic effect and a more cytotoxic effect on HepG2 cells. This combination significantly increased apoptosis and ROS levels compared to treatment alone with NaB or calcitriol. Gene expression and proteomics analysis revealed inhibition of DNA replication and the cell cycle process, further confirming the potent anti-proliferative effects of the combination therapy. When HepG2 cells were treated with a combination of 3.3mM NaB and 1µM calcitriol, mRNA levels of apoptosis-related genes AKT1 and MDM2 were downregulated, while p53 was upregulated. Additionally, cell cycle-related genes CDKN1A, GADD45A, and p27 were upregulated, whereas MCM2, MCM5, and MCM7 were downregulated. Furthermore, genes associated with the vitamin D receptor (VDR), including VDR and CYP24A1, were upregulated, while CYP27B1 was downregulated. Our proteomic analysis revealed decreased MCM2 and MCM5 protein expressions which was confirmed by western blotting. In conclusion, this study highlights the potential of NaB and calcitriol as a promising therapeutic strategy for HCC.

Novel anti-tumor effect of natural products from Aloe vera resin and their in-vitro/in-silico targeting mechanism of carbonic anhydrase-II and IX.

Human carbonic anhydrase (hCA) plays a vital role in the development and progression of tumors in hypoxic conditions. Herein we report the hCA-II and hCA-IX activities of natural products isolated from Aloe vera (L.) Burm.f., to know their potential in tumors. These isolated compounds (1-10) displayed varying degrees of inhibition against hCA-II and hCA-IX. All the compounds showed potent activity against hCA-IX with IC50 values in the range of 2.9 - 29.1 µM. While for hCA-II, compounds 1, 2, 5-10 exhibited IC50 in the range of 4.7 - 23.4 µM. The most effective hCA IX and II inhibitors, 2 and 5, were chosen for in vitro mechanism studies, revealing that they are competitive inhibitors. Furthermore, when tested for their cytotoxic effect on BJ (normal) cell line, all the compounds showed no cytotoxic behavior, while on Prostate cancer cells (PC-3), compounds 1, 3, 5, 7, and 9 exhibited significant antiproliferative activity. Molecular docking was also conducted within the hCA IX and hCA-II active sites to observe their binding capability. Compounds 1, 5, 7, and 9 were active against both isozymes of hCA and in the PC-3 cell line, therefore these are the best choices for further in vivo studies..

A systematic review of lithium biology and pharmacology and toxicological evaluation of new organic lithium salts

Objective: to systematize scientific data on biomedical studies investigating trace element lithium over the past 70 years; evaluate toxic properties of lithium ascorbate (LiAsc) as an important promising candidate molecule.Material and methods. An analysis of 49,959 publications on lithium biomedical research retrieved from PubMed/MEDLINE database was carried out using modern data mining methods developed within the framework of topological approach to recognizing (Yu.I. Zhuravlev scientific school). Publications found by experts and not indexed in PubMed/MEDLINE were used in discussing the results of a systematic analysis of publications array retrieved from PubMed/MEDLINE. An experimental study of chronic 180 day-long LiAsc (at doses of 5, 50 and 150 mg/kg) toxicity was performed on 36 “Soviet chinchilla” rabbits by assessing local irritant action. Intoxication clinical picture, body weight dynamics, water and food intake as well as physiological, hematological and biochemical parameters were analyzed.Results. Classification and systematization of all currently available publications on lithium biology and medicine were performed. It was shown that pharmacological applications of lithium salts in mental disorders as well as lithium effects on simple sugars metabolism, lipid metabolism, blood pressure regulation, hematopoiesis, inflammation and tumor growth inhibition, neurotransmitter homeostasis, neurotrophic and neuroprotective molecular mechanisms as well as homeostasis of other electrolytes comprised promising fields of lithium drug research. The prospects for using organic lithium salts, particularly LiAsc, for various therapeutic goals were also discussed. 180-day-long oral administration of LiAsc at doses of 5, 50, 150 mg/kg resulted in no macroscopic signs of local inflammatory reaction while examining its local irritant effect.Conclusion. The lithium-ion effect on neurotransmitters promotes neuroprotection and reduces a risk of addiction. The antihypertensive, antiatherosclerotic, antidiabetic, antitumor and neurotrophic effects related to organic lithium salts may be beneficial in various therapeutic applications.

Synthesis, Characterization, DFT Calculations, and Pharmacological Activity of Azo Dye Ligand and Its Cu(II) Complex Comprising Nitrogen and Oxygen Donor Atoms

ABSTRACTCoupling the diazonium salt of sulfadiazine with dibenzoylmethane afforded the 4‐(2‐(1,3‐dioxo‐1,3‐diphenylpropan‐2‐ylidene)hydrazinyl)‐N‐(pyrimidin‐2‐yl)benzene sulfonamide ligand (HL). The ligand (HL) and its Cu(II) complex structure have been investigated via magnetic attraction testing, TGA, FTIR, UV–visible, XRD, and CHN analyses. The spectrum data indicate that the ligand demonstrates monobasic bidentate behavior via deprotonating opposite the oxygen atom of the carbonyl (CO) group and linking using the NH of the hydrazone group (NNH). Copper (II) complex present in octahedral structure. A number of TGA steps (Ea, A, ΔH*, ΔS*, and ΔG*) had their dynamical characteristics computed and described using the Coats–Redfern and Horowitz–Metzger formulas. Molecular studio programmer was utilized to perform density functional theory (DFT) calculations in order to investigate the ideal configuration of HL and its Cu(II) complex. The HL and its copper (II) complex exhibited antitumor effects against MCF‐7 and HepG‐2 cell lines. Furthermore, the width of the inhibition zone was employed to evaluate the in vitro antibacterial effect of HL and a specific complex towards Gram‐negative organisms Escherichia coli (E. coli) and Gram‐positive organisms Staphylococcus aureus. The ligand and its Cu(II) complex were examined using both the viscosity and spectrum of absorption of calf thymus DNA binding experiments.

Homeostatic nanomedicine: Protein S-nitrosylation dyshomeostasis dominated oncotherapy based on a tumor-microenvironment-activated nanoparticle

Nitric oxide (NO) holds promise as a therapeutic agent in oncotherapy, yet its efficacy is hindered by low bioavailability, concentration-dependency, and tumor resistance to nitrosative stress. To overcome these limitations, herein, we propose a novel strategy aimed at specifically breaking the protein S-nitrosylation homeostasis of tumors. An acid-responsive nanoplatform comprising amorphous iron / mesoporous silica (AMSP) is constructed to orchestrate synergistic anti-tumor effect of Fe2+ and NO. Activating by the tumor microenvironment, nanopores of AMSP facilitate the in-situ generation of dinitrosyl iron complexes, promoting the physiological stability of NO and protein S-nitrosylation via transnitrosylation. Moreover, the released Fe2+ accelerate reactive oxygen species accumulation in tumor cells, which not only derives stronger nitrating reagents, but also inhibits the denitrosylation reaction triggered by tumor-expressed reducing species. The multiple effects of AMSP induce excessive cellular S-nitrosylation, thereby guiding an untraditional apoptotic pathway, glyceraldehyde-3-phosphate dehydrogenase S-nitrosylation mediated nuclear translocation and protein degradation. Overall, our findings offer a new paradigm of homeostatic nanomedicine, potentially advancing oncotherapy modalities.

Delivery of IL2RG mRNA via nanoparticles to enhance CD8+ T cell promotes anti-tumor effects against late-stage triple-negative breast cancer

BackgroundThe manipulation of CD8+ T cell functions through genetic modifications presents a novel approach to cancer immunotherapy. This study aimed to explore the effects of IL2RG-overexpressing CD8+ T cells and assess the efficacy of delivering IL2RG mRNA via nanoparticles (NPs) to the tumor microenvironment in triple-negative breast cancer (TNBC).MethodsSingle-cell RNA sequencing (scRNA-seq) was conducted on tissue from early and late-stage TNBC, followed by a meta-analysis of six breast cancer arrays from the GEO database to identify candidate genes. CRISPR/Cas9 was employed for gene knockout and overexpression in CD8+ T cells, which were then analyzed using flow cytometry, ELISA, immunofluorescence, and metabolic assays. A 3D cancer cell spheroid model was used for co-culture experiments. Lipid-coated calcium-phosphate (LCP)@IL2RG NPs were synthesized and injected into TNBC mouse models.ResultsIL2RG was identified as significantly associated with late-stage TNBC. Overexpression of IL2RG in CD8+ T cells led to increased cell activation, cytotoxicity, and glycolysis, while knockout reduced these effects. Overexpressing IL2RG in CD8+ T cells co-cultured with 3D cancer spheroids resulted in enhanced apoptosis and reduced cancer cell invasion. Injection of LCP@IL2RG NPs into TNBC mouse models significantly mitigated tumor growth.ConclusionsOverexpressing IL2RG in CD8+ T cells enhances tumor immunotherapy. Delivering IL2RG mRNA via NPs further amplifies this effect, offering a promising strategy for the treatment of late-stage TNBC.

Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer

In clinical practice, the limited efficacy of standard comprehensive therapy for advanced bladder cancer and the lack of targeted treatment options are well recognized. Targeting abnormal epigenetic modifications in tumors has shown considerable potential in cancer therapy. Through drug screening in tumor organoids, we identified that ML324, a histone lysine demethylase 4A (KDM4A) inhibitor, exhibits potent antitumor effects in both in vitro and in vivo cancer models. Mechanistically, Kdm4a demethylates H3K9me3, leading to chromatin opening and increased accessibility of Gabpa to the squalene epoxidase (Sqle) gene promoter, resulting in transcriptional activation. Inhibition of Kdm4a downregulates Sqle transcription, blocking cholesterol synthesis and causing squalene (SQA) accumulation. This process induces reactive oxygen species (ROS) clearance and suppresses JNK/c-Jun phosphorylation, ultimately inducing apoptosis. Furthermore, ML324 treatment significantly inhibited tumor growth in bladder cancer patient-derived xenograft (PDX) models. Our findings reveal the presence of a Kdm4a-Sqle-ROS-JNK/c-Jun signaling axis that regulates oxidative stress balance, offering a novel strategy for targeted therapy in bladder cancer.

Poly (ADP-Ribose) Polymerase 1 Induces Cyclic GMP-AMP Synthase-stimulator of Interferon Genes Pathway Dysregulation to Promote Immune Escape of Colorectal Cancer Cells

Colorectal cancer (CRC) ranks third globally in cancer incidence and mortality, posing a significant human concern. Recent advancements in immunotherapy are noteworthy. This study explores immune modulation for CRC treatment. Initially targeting poly (ADP-ribose) polymerase 1 (PARP-1), a gene overexpressed in CRC tissues per The Cancer Genome Atlas, we examined its correlation with immune cell infiltration using the Tumor Immune Estimation Resource tool. Quantitative reverse transcription polymerase chain reaction assessed PARP-1 mRNA and inflammation-related gene expression in tumor tissues and cells. Assessing CD8+ T-cell proliferation and cytotoxicity towards HCT116 cells involved carboxyfluorescein diacetate succinimidyl ester and lactate dehydrogenase kits. Chemotaxis was gauged using a Transwell system in a CD8+ T-cell coculture setup, with immunofluorescence revealing cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) levels in HCT116 cells. Enzyme-linked immunosorbent assay kits measured CD8+ T-cell cytokine secretion. The findings suggested that PARP-1 was overexpressed in CRC tissues and cells and this overexpression was positively correlated with Treg cell infiltration. Overexpression of PARP-1 could significantly reduce the proportion of cGAS and STING-positive cells in HCT116 cells, dampen the proliferation, tumor-killing capacity, and chemotaxis of CD8+ T cells, and inhibit the secretion of related cytokines. The introduction of STING agonists could reverse the effects caused by overexpressed PARP-1. In vivo experiments affirmed the independent anti-tumor effects of PARP-1 inhibitors and STING agonists, synergistically inhibiting tumor growth. Silencing PARP-1 in HCT116 cells potentially boosts CD8+ T-cell activity against these cells through the cGAS-STING pathway.

Preliminary Assessment of the Protective and Antitumor Effects of Several Phytoene-Containing Bacterial and Microalgal Extracts in Colorectal Cancer

The identification of new functional food constituents is a priority to improve the prognosis and prevention of colorectal cancer (CRC). In this study, several bacterial and algal phytoene-enriched extracts were obtained, and their potential activity against oxidative damage and their ability to inhibit proliferation and cell migration in several human colon-adenocarcinoma-derived cell lines were assessed. The main conclusions indicate that total extracts of Sphingomonas echinoides and Chlorella sorokiniana exhibited the highest protective effect against oxidative damage. All extracts enhanced the activity of detoxifying enzymes, particularly importantly the increase of NAD(P)H:quinone oxidoreductase activity, which reached a value 40% higher than that of untreated control cells upon exposure to Escherichia coli extracts. Staphylococcus haemolyticus and transgenic E. coli extracts significantly arrested the migration capacity of both cell lines, while S. haemolyticus and C. sorokiniana extracts inhibited cell proliferation by 15 to 20% compared to untreated cells. These results point to these extracts as potential antioxidant complements able to protect cells against oxidative damage and with a moderate ability to inhibit the proliferation and migration of CRC tumor cells, paving the way to design functional foods or probiotic formulations with preventive properties against oxidative stress-related diseases, such as cancer, or as starting point for purifying anticancer compounds.

Potential Anti-tumor Effects and Apoptosis-Inducing Mechanisms of Saponins: A Review.

The search for effective cancer therapies highlights saponins, natural plant-derived compounds, as promising anticancer agents. These compounds induce apoptosis in cancer cells by activating caspases, essential enzymes for cell death. For example, Soyasapogenol B from Glycine max and Astragaloside IV from Astragalus membranaceus effectively trigger apoptosis in cancer cells. Additionally, saponins, such as Compound K from American ginseng and Saikosaponin from Bupleurum falcatum, affect extrinsic and intrinsic pathways, including mitochondrial release of cytochrome C and activation of caspase-9. Ziyuglycoside II also acts on both pathways and activates the ROS/JNK pathway. Understanding these mechanisms provides promising prospects for developing more specific and safer anticancer therapies. The review utilized the ScienceDirect, PubMed, and Google Scholar databases. It was found that original articles and reviews from journals indexed in these sources emphasized the antitumor capabilities of saponins and discussed their role in apoptosis induction and caspase activation. The activation of caspases by saponins in the apoptotic pathway involves two main pathways: the extrinsic pathway is initiated by external signals that activate caspase-8, while the intrinsic pathway starts with internal stimuli, causing the release of cytochrome c and the activation of caspase-9. These pathways both lead to the activation of effector caspases (caspases 3, 6, and 7), culminating in apoptosis, an essential process for maintaining cellular balance and eliminating damaged cells. Identifying saponins in the context of cancer and their mechanisms of action is an ever-evolving field. Future research may lead to more targeted and personalized therapies, highlighting the collaboration between basic and clinical research in this promising area of medicine.

A pH-Sensitive cRGD-PEG-siRNA Conjugated Compound Targeting Glioblastoma.

Glioblastoma ranks among the most prevalent primary intracranial tumors, characterized by high mortality and poor prognosis. Chemotherapy remains a key treatment strategy for gliomas, though most current drugs suffer from limited efficacy and significant toxicity. This study focuses on a cRGD-siEGFR coupling compound synthesized in a previous stage. Prior research indicated that cRGD-siEGFR molecules exhibited certain targeting and antitumor properties but faced issues of inadequate targeting, low efficacy, and high renal toxicity. To enhance antitumor efficacy and mitigate side effects, a pH-responsive, long-circulating, and highly targeted siRNA delivery system, the cRGD-PEG-siEGFR conjugate, was developed. The targeting, antitumor effects, and biological distribution of cRGD-PEG-siEGFR were examined. The results demonstrated that cRGD-PEG-siEGFR was effectively taken up by αvβ3-positive U87MG cells, specifically silenced EGFR gene expression, and exhibited antitumor effects. In normal physiological conditions, it avoided uptake by normal cells, thereby reducing side effects. Furthermore, in vivo biodistribution experiments revealed that cRGD-PEG-siEGFR, compared to cRGD-siEGFR, significantly decreased renal accumulation and exhibited prolonged circulation. Consequently, cRGD-PEG-siRNA emerges as a promising drug candidate with attributes of long circulation, high targeting, pH responsiveness, and substantial antitumor efficacy.

Research Progress in the Medicine-Food Dual Use of Astragalus for Gastrointestinal Tumors.

Gastrointestinal tumors have a major impact on human life expectancy and quality of life and are a major cause of personal and social hygiene stress. Gastrointestinal tumors are the main cause of cancer-related death, and the main treatment methods are surgery, radiotherapy, and chemotherapy. However, they also cause great damage to the body and have a poor prognosis after surgery. Therefore, we urgently need safe and effective drugs to intervene in gastrointestinal tumors. In recent years, Traditional Chinese Medicine has been widely used in tumor treatment as a complementary and alternative therapy. Astragalus membranaceus is one of the main herbal medicines with tonic effect and one of the important components of many antitumor herbal compounds. Astragalus polysaccharides, saponins, and flavonoids are the main active components of Astragalus, all of which have antitumor effects. In this article, we studied the mechanism of action of Astragalus and its active ingredients in the intervention of gastrointestinal tumors in recent years and suggested a new approach for the study of Astragalus intervention in gastrointestinal tumors from the perspective of the homology of medicine and food.

Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity

S100A9, a multifunctional protein mainly expressed by neutrophils and monocytes, poses an immunological paradox. In virus infections or sterile inflammation, it functions as an alarmin attracting innate immune cells, as well as mediating proinflammatory effects through TLR4 signaling. However, in cancer, S100A9 levels have been shown to associate with poor prognosis and lack of response to immunotherapy. Its expression by myeloid cells has been related to an immune suppressive phenotype, the so-called myeloid derived suppressor cells (MDSCs). Targeting S100A9 in cancer has therefore been proposed as a potential way to relieve myeloid-mediated immune suppression. Surprisingly, we found that blocking the extracellular TLR4 signaling from S100A9 using the inhibitor Paquinimod, resulted in increased tumor growth and a detrimental effect on anti-PD-L1 efficacy in the CT26 tumor model. This effect was caused by a reduction in the tumor immune infiltration to about half of untreated controls, and the reduction was made up of a 5-fold decrease in Ly6Chigh monocytic cells. The suppressive Ly6G+ myeloid cells compartment was not reduced by Paquinimod treatment, suggesting alternative mechanisms by which S100A9 contributes to myeloid-mediated suppression. Intratumoral injection of recombinant S100A9 early after mice inoculation with CT26 cells had an anti-tumor effect. These findings indicate an important yet understudied role of S100A9 as an alarmin and immune stimulatory signal in cancer settings, and highlight the potential to exploit such signals to promote beneficial anti-tumor responses.

Multifunctional nanomaterials composed entirely of active pharmaceutical ingredients for synergistically enhanced antitumor and antibacterial effects

IntroductionMultifunctional nanomaterials are emerging as promising tools for treating both cancer and bacterial infections. However, integrating dual therapeutic capabilities into a single system remains challenging. This study presents multifunctional nanoparticles (ECI-NPs) based on Epigallocatechin gallate (EGCG) oligomers, Curcumin (CUR), and Indocyanine Green (ICG) for combined cancer and bacterial treatment.MethodsECI-NPs were synthesized via oxidative coupling of EGCG, CUR, and ICG. The nanoparticles were characterized for stability, size, drug loading, and release profiles. Cellular uptake, phototoxicity in melanoma cells, and antibacterial activity against Escherichia coli and Staphylococcus aureus were also evaluated.ResultsECI-NPs demonstrated optimal stability, high drug loading, and controlled release. Cellular studies showed increased uptake and greater phototoxicity in melanoma cells compared to free drugs. ECI-NPs also exhibited enhanced anticancer effects and strong antibacterial activity, outperforming the individual components.DiscussionThe polyphenol-based ECI-NPs offer synergistic therapeutic effects, overcoming the limitations of free drugs in terms of solubility and efficacy. This dual-function platform shows potential for broader biomedical applications, addressing challenges in cancer and bacterial infections. Further research will focus on in vivo studies and clinical translation.

Salmonella Biomimetic Nanoparticles for Photothermal-Chemotherapy of Colorectal Cancer.

Nanomedicines have been widely used in colorectal cancer treatment, but their suboptimal targeting and deficient penetration capabilities remain obstacles in the delivery of therapeutics. In this study, inspired by the natural tumor tropism and intestinal invasion of Salmonella, we engineered highly biomimetic nanoparticles (SM-AuNRs) utilizing a Salmonella membrane to coat bacilliform Au nanorods. The engineered SM-AuNRs were able to mimic the germ's morphology and biological surface. SM-AuNRs containing the specific proteins inherited from the Salmonella membrane facilitated specific targeting and internalization into tumor cells. Meanwhile, SM-AuNRs with the rod-shaped morphology effectively traversed mucus barriers and tumor stroma. Due to the superior biological barrier penetrating and tumor targeting capabilities, doxorubicin-loaded SM-AuNRs with near-infrared laser irradiation displayed remarkable photothermal-chemotherapeutic antitumor effects in mouse orthotopic colorectal cancer models. Our findings pave the way for the design of bacteria-mimicking nanoparticles, presenting a promising avenue for the targeting and efficient treatment of colorectal cancer.

Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy.

The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.

Anti-tumor effects of ellagic acid and mesenchymal stem cell-conditioned medium on breast cancer cells on the 3D printed PCL/agarose scaffolds

Numerous investigations have demonstrated that natural bioactive compounds, such as flavonoids, exhibit synergistic effects with anticancer agents utilized in clinical practice. Stem cell therapies play a critical role in the domain of oncology; nevertheless, conflicting results have surfaced regarding the potential pro-cancer or anti-cancer characteristics of mesenchymal stem cells. The primary aim of the current investigation was to examine the anticancer efficacy of ellagic acid (EA) alone or in combination with adipose tissue stem cells derived conditioned medium (ADSCs-CM) on human breast cancer cells. In order to overcome the potential effects of two-dimensional (2D) culture, a three-dimensional (3D) printed polycaprolactone (PCL)/agarose scaffold is utilized to evaluate cancer cell behavior. More recently it was reported this scaffold had open and interconnected pores, as well as good water absorption and mechanical properties. Assessment of MCF-7 cancer cell viability was conducted through MTT assay, flow cytometry, cell cycle assay, and quantitative real-time PCR within a 3D cell culture framework. The outcomes revealed a reduction in cancer cell viability across all treatment cohorts in comparison to the control group. Particularly noteworthy was the significantly enhanced effect of the EA and CM combination relative to each component administered individually. Flow cytometry assessment using annexin V/PI staining indicated a decrease in cancer cells, particularly evident in the combination-treated group. Furthermore, the mRNA expression levels of BAX, BCL2, vascular endothelial growth factor (VEGF), and caspase 3 genes were consistent with pathways associated with apoptosis. Consequently, the synergistic anti-proliferative impact of EA in conjunction with ADSCs-CM on MCF-7 cells has been substantiated. These findings have two important implications for breast cancer research; highlight the utility of the PCL/agarose scaffold as a cancer model and suggest new avenues for the development of adjuvant anticancer therapeutic approaches.

Antitumor effect of the Newcastle disease virus strain NDV/Altai/pigeon/777/2010 on a model of solid Lewis carcinoma

Aim. To evaluate the efficacy of intratumoral administrations of the Newcastle disease virus strain NDV/Altai/pigeon/777/2010, to compare progression of the tumor nodes after virotherapy and to analyse pathomorphological changes in the tumor tissue in vitro and in vivo. Single intratumoral injections of the mesogenic strain of Newcastle disease virus NDV/Altai/pigeon/777/2010, isolated from a rock dove in Siberia, were done into outbred mice of the C57Bl/6 line into solid nodes of Lewis lung carcinoma that were grafted subcutaneously. Then the dynamics of tumor growth and pathomorphological changes in the tumor tissue were assessed and analyzed.It was shown that single intratumoral injections into immunocompetent C57Bl/6 mice with the mesogenic strain of Newcastle disease virus NDV/Altai/pigeon/777/2010 led to an increase in peculiar pathomorphological changes in the tumor tissue of subcutaneously grafted Lewis lung carcinoma and to a decrease in tumor growth compared to the control group of mice in vivo. A direct cytotoxic effect of the NDV strain on the Vero E6 cell line in vitro was noted.The results of this study indicate that the NDV strain NDV/Altai/pigeon/777/2010 has antitumor properties. This may enable clinical trials to prove its effectiveness as an antitumor drug.