Anticancer Effects Research Articles

Vitamin D3 reduces the expression of M1 and M2 macrophage markers in breast cancer patients.

Vitamin D3 (VD) is known for its immunomodulatory and anticancer effects. This study aimed to characterize tumor-associated macrophages (TAMs) in breast cancer (BC) and assess the influence of VD and its active metabolite, calcitriol, on their polarization. TAMs were isolated from BC patients and characterized. Monocytes were differentiated into macrophage classes (M0, M1, M2a, M2c) and treated ex vivo with calcitriol. The expression of VD-related proteins in tumor tissue was correlated with TAMs and monocyte-derived macrophages (MDMs) characteristics. TAM expression of CD200R, CD204, CD80, HLA-DR, and CD44 was negatively correlated with CYP27B1 in selected patient groups. Patients with high CYP27B1 tumor expression showed significantly lower CD200R, CD204, and CD44 expression. In patients with normal VD levels and premenopausal, CD80 expression in M2a and M2c MDMs (control, untreated ex vivo with calcitriol) was negatively correlated with plasma VD. Calcitriol reduced HLA-DR during MDM differentiation in all patients; CD80 decrease significantly except in patients with normal VD levels or metastasis. Calcitriol also decreased CD163 expression. The decrease in both M1 and M2 macrophage markers by calcitriol or their negative correlation with CYP27B1 indicate the modulatory, but rather anticancer activity of VD. The intensity of these effects was the strongest in postmenopausal patients and those without metastases.

An Overview of the Phytochemical and Therapeutic Potential of Wrightia Tinctoria

Introduction: Several natural phytomedicines derived from Chinese herbs demonstrate a wide range of pharmacological effects. Wrightia tinctoria (WT) is a small deciduous tree known as sweet indrajao. It belongs to the Apocynaceae family. Many diseases have been treated with this plant's phytoconstituents, such as skin disorders, dysenteric, diarrhea, and hair treatments. In addition, the therapeutic elements of WT demonstrate significant anti-inflammatory and anti-dandruff properties. However, there is a difference between this plant's preclinical and clinical significance. The purpose of this study is to collect and evaluate the various chemical, medicinal, and pharmacological characteristics of WT in relation to multiple disorders using preclinical evidence. This will serve as a valuable foundation for researchers to explore its effectiveness in clinical trials further. Materials and Methods: A comprehensive search was conducted across several databases, including PubMed, Web of Science, Scopus, Academic Journals Embase, Google Scholar, and Science Direct. The search utilized specific keywords such as "Wrightia tinctoria" as well as terms like "Traditional Chinese Medicine," "Pharmacological activities," "Anti-cancer," "Anti-viral," "Anti-microbial," "Anti-psoriatic," "Anti-Inflammatory," "Quercetin" and their combinations mainly from 1993 to 2024. Results: The pharmacological and therapeutic potential of WT is gathered and summarized based on existing research reports. WT substances consist of various phytoconstituents, including flavonoids, steroids, alkaloids, volatile oils, esters, and others. These components are primarily responsible for the various pharmacological effects of WT, such as anti-oxidant, anti-bacterial, antifungal, anti-diabetic, anti-cancer, anti-microbial, anti-inflammatory, and anti-ulcer effects. Conclusion: This review focuses on current research findings regarding WT's therapeutic potential and pharmacological activities. Additionally, it addresses the major safety and toxicity issues related to WT.

Modulating the unfolded protein response with ISRIB mitigates cisplatin ototoxicity

Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin, and UPR marker gene expression and cell death measured. Treatment with ISRIB (Integrated Stress Response InhIBitor), a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested for its ability to reduce apoptosis in HEK cells, hair-cell death in cochlear cultures, and hearing loss using an in vivo mouse model of cisplatin ototoxicity. Finally, to evaluate whether ISRIB might interfere with cisplatin chemoeffectiveness, we tested it in head and neck squamous cell carcinoma (HNSCC) cell-based assays of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose–response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatin’s cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.

Heterocyclic Phytochemicals as Anticancer Agents.

Cancer continues to be a major global health challenge, driving the need for the discovery of novel therapeutic agents. Among these, heterocyclic phytochemicals have gained significant attention for their potential as anticancer agents. This review offers a detailed analysis of various classes of heterocyclic compounds with proven anticancer properties, shedding light on their mechanisms of action. The study draws from a diverse array of natural product sources, detailing the chemical structures and bioactivities of these compounds. Key heterocyclic classes such as alkaloids, flavonoids, coumarins, and terpenoids are emphasized due to their potent anticancer effects. Heterocyclic phytochemicals exhibit diverse anticancer mechanisms, including the modulation of cellular pathways like apoptosis, angiogenesis, and cell cycle progression. The combination of heterocyclic phytochemicals with conventional cancer therapies has shown promising synergistic effects, enhanced treatment efficacy and reducing side effects. The review systematically evaluates both preclinical and clinical studies, revealing the efficacy, safety profiles, and pharmacokinetics of selected heterocyclic compounds. The promising outcomes highlighted in this review underscore the critical need for ongoing research to fully realize the therapeutic potential of heterocyclic phytochemicals in cancer treatment.

Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy

Fifty-two years have passed since President Nixon launched the “War on Cancer”. Despite unparalleled efforts and funds allocated worldwide, the outlined goals were not achieved because cancer treatment approaches such as chemotherapy, radiation therapy, hormonal and targeted therapies have not fully met the expectations. Based on the recent literature, a new direction in cancer therapy can be proposed which targets connections between cancer cells and their microenvironment by chemical means. Cancer–stromal synapses such as immunological synapses between cancer and immune cells provide an attractive target for this approach. Such synapses form ligand–receptor clusters on the interface of the interacting cells. They share a common property of involving intercellular clusters of spatially proximate and cooperatively acting proteins. Synapses provide the space for the focused intercellular signaling molecules exchange. Thus, the disassembly of cancer–stromal synapses may potentially cause the collapse of various tumors. Additionally, the clustered arrangement of synapse components offers opportunities to enhance treatment safety and precision by using targeted crosslinking chemical agents which may inactivate cancer synapses even in reduced concentrations. Furthermore, attaching a cleavable cell-permeable toxic agent(s) to a crosslinker may further enhance the anti-cancer effect of such therapeutics. The highlighted approach promises to be universal, relatively simple and cost-efficient. We also hope that, unlike chemotherapeutic and immune drugs that interact with a single target, by using supramolecular large clusters that include many different components as a target, the emergence of a resistance characteristic of chemo- and immunotherapy is extremely unlikely.

Ang-1 promotes tumorigenesis and mediates the anti-cancer effects of Artesunate on Choroidal melanoma via the regulation of Akt/mTOR signaling pathway

The impact of Ang-1 on tumors remains a subject of contention, with its mechanism of action exhibiting complexity in the progression of diverse tumor types. Ang-1 has been shown to promote the progression of glioma, glioma, esophageal and human cervical cancer, whereas it exerts inhibitory effects on the growth of breast and colon cancer. However, the specific function of Ang-1 in CM has not been clarified. This research aims to explore the function of Ang-1 on CM and the underlying mechanism. WB and qPCR were utilized to measure the expression levels of different factors in CM cells. Clonogenic, CCK-8 and Transwell migration assay were used to probe CM cells’ proliferation and migration ability. Xenograft tumor model was used to testify the effect of Ang-1 and Artesunate (ART) on the growth of CM in vivo. We found Ang-1 promoted CM proliferation and migration, while it was inhibited by ART in vitro. Moreover, both ART treatment and Ang-1 knockdown had the effect of suppressing tumor growth in CM xenograft model. Mechanically, Ang-1 activated Akt/mTOR pathway and induced epithelial-mesenchymal transition (EMT) in CM cells. Furthermore, ART regulated Akt/mTOR pathway by decreasing the expression of Ang-1 in CM cells. Ang-1 promotes tumorigenesis of CM by regulating Akt/mTOR pathway, which can be inhibited by ART.

Modulation of PRC1 Promotes Anticancer Effects in Pancreatic Cancer

Modulation of PRC1 Promotes Anticancer Effects in Pancreatic Cancer

Plant-derived glycosides in cancer treatment: diverse strategies for tumor suppression

Plant-derived glycosides have emerged as promising candidates for cancer therapy due to their diverse biological activities. These compounds exert their anti-cancer effects through multiple mechanisms, including apoptosis induction, cell cycle arrest, inhibition of angiogenesis, suppression of metastasis, and immune modulation. Cardiac glycosides, flavonoid glycosides, and saponins are among the key types of glycosides showing potential in preclinical studies. By selectively targeting cancer cells, these glycosides demonstrate the ability to induce programmed cell death and interfere with cancer progression without harming normal cells. In addition, their role in inhibiting blood vessel formation and reducing cancer cell spread positions them as valuable components of future cancer treatment strategies. Preclinical evidence, supported by emerging clinical data, underscores the potential of plant-derived glycosides as novel agents in oncology, either as standalone treatments or in combination with conventional therapies. Ongoing research will determine their full therapeutic potential in cancer management.

Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment.

Prostate cancer (PCa) has high morbidity and mortality rates in elderly men. With a history of thousands of years, traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis, enhance therapeutic effects, and reduce the risk of recurrence and metastasis. Multiple studies have shown that Coridius chinensis (Cc) has anticancer effects. To elucidate the mechanism of action of Cc against PCa via network pharmacology and molecular docking. Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software, the PharmMapper database and the GeneCards database. Then, the STRING database was used to construct the protein-protein interaction network. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and molecular docking analyses were subsequently conducted to identify the key targets, active ingredients and pathways involved. GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway (P value < 1.0 × 10-8). Multiple targeting ingredients that can affect multiple pathways in PCa have been identified in Cc. Seven active compounds (asponguanosines A, asponguanine B, asponguanine C, aspongpyrazine A, N-acetyldopamine, aspongadenine B and aspongpyrazine B) were selected for molecular docking with 9 potential targets, and the results revealed that aspongpyrazine A and asponguanosine A are the main components by which Cc affects PCa (affinity<-5 kcal/mol, hydrogen bonding), but more studies are needed. We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa, supporting the development of Cc as a natural anticancer agent.

Black Tea Suppresses Invasiveness and Reverses TNF-α-Induced Invasiveness and Cell Stemness in Human Malignant Melanoma Cells.

Invasiveness and epithelial-mesenchymal transition (EMT) are main patterns of metastatic disease, which is the major cause cancer-related mortality in human malignant melanoma cells. Tea and its consumption extract are associated with a lower risk of several types of cancer and have anti-inflammatory and antioxidative biological effects. However, the anti-EMT and anti-cancer stemness effect of black tea ethanol extracts (BTEE) in human melanoma remain poorly understood. In this study, the effects of BTEE-reduced invasiveness, EMT, and cancer stemness were evaluated in human A 375 and A2058 melanoma cells. BTEE inhibited the activity of u-PA, migration, and invasiveness by repressing p-FAK signaling pathway. BTEE affected the EMT by downregulating the expression of β-catenin, N-cadherin, fibronectin, vimentin, and Twist-1. BTEE also reduced tumor necrosis factor-alpha (TNF-α)-induced invasiveness and cancer stemness characteristics in vitro. The growth of melanoma in nude mice xenograft model showed that BTEE suppressed A 375 tumor growth in vivo.

Mechanisms of Action of the Herba Salviae Chinensis-Fructus Akebiae Pair in the Treatment of Non-small Cell Lung Cancer based on a Network Pharmacology Study

Objective: To study the active ingredients and mechanism of action of "Herba Salviae Chinensis-Fructus Akebiae" drug pair in the treatment of non-small cell lung cancer (NSCLC) by using network pharmacology to provide theoretical basis for clinical application. Methods: The TCMSP (Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform) was used to obtain the active ingredients and targets of "Herba Salviae Chinensis-Fructus Akebiae", and the results were analyzed by the Genecard (https://genecard, org/) database, the Online Mendelian Inheritance Network (OMI), the Genecard database, the Genecard database, and the Online Mendelian Inheritance Network. We searched the Genecard (https://genecard, org/) database and the Online Mendelian Inheritance in Man (OMIM) database (http://omim. org/) for non-small cell lung cancer (NSCLC) disease targets by selecting "NSCLC" as a keyword, and then obtained the results of the "Herba Salviae Chinensis-Fructus Akebiae" drug pair by using venn. We used venn to obtain the intersecting targets of the drug pair "Herba Salviae Chinensis-Fructus Akebiae" and NSCLC, and then used the STRING database and Cytoscape to construct a common target visualization network diagram. The gene (GO) enrichment analysis and KEGG enrichment analysis were realized with the help of metascape database and Microbiology platform. Results: Five active ingredients of Ishiminokan-Precipitant were obtained, and 3695 non-small cell lung cancer targets and 123 common targets were obtained. GO analysis showed that the process of GO enrichment was mainly related to the regulation of responses to inorganic substances, transcriptional regulatory complexes, cytokine receptor binding, etc. KEGG enrichment showed that the process of KEGG enrichment was mainly through Pathways in Cancer, ILRT, and cytokine receptor binding. KEGG enrichment showed that KEGG mainly exerted anti-cancer effects through pathways in cancer and IL-17 signaling pathway. Conclusion: Using the method of network pharmacology, it is proved that the drug pair "Herba Salviae Chinensis-Fructus Akebiae" can exert therapeutic effects on NSCLC through multi-components, multi-targets, and multi-pathways, and provides the theoretical basis for the clinical application.

Novel Pseudomonas putida-derived nanoliposomes enhance the inhibition of MCF-7 breast cancer cells by superb intracellular uptake of doxorubicin

In this study, we aimed to utilize phospholipids from the bacterium Pseudomonas putida (PP) as a plentiful, safe, and accessible resource for creating nanoliposomes to deliver doxorubicin (Dox) to MCF-7 breast cancer cells. This bacterium provides a cost-effective source of phospholipids commonly used in nanoliposome production, with no toxicity or adverse environmental impact. To this end, molecular dynamics (MD) simulations were first conducted to evaluate the feasibility of this approach and to analyze the behavior and interaction of Dox with the nanoliposomes. The phospholipids of PP were then extracted using Folch's technique. Subsequently, Dox-loaded PP-derived nanoliposomes (PNL-Dox) were developed using the thin-film method. The physicochemical properties of the fabricated nanocarrier were then investigated and the anticancer effects of this system were tested on MCF-7 cells. The results of the MD simulations indicated that Dox reacted with all of the phospholipids through hydrogen bonds without affecting the fluidity, stability, and thickness of the nanoliposome membrane. Additionally, a small number of Dox molecules interacted with the nanocarrier membrane, while the remaining were located in its interior. The physicochemical investigation results showed that PNL-Dox had an average particle size and zeta potential of 271.7 ± 7.1 nm and −8.8 ± 3.3 mV, respectively. Scanning electron microscopy revealed that the particles were spherical and did not show any signs of aggregation. Drug release of PNL-Dox was gradual at pH 7.4 and 6.5, with a significantly higher release at pH 6.5. In vitro studies demonstrated successful uptake of PNL-Dox by MCF-7 cells, resulting in cytotoxicity within 24 and 48 h of treatment. Also, it increased apoptosis and reduced the production of reactive oxygen species (ROS) in these cells. Our study showcased the potential of PP phospholipids to form a promising anti-cancer drug delivery system, opening up new possibilities for the treatment of all types of cancers.

Synthesis of thiophene hydrazone derivatives by Japp Klinegmann reaction method for anticancer activity against MCF-7 cell line.

The creation of novel anticancer drugs is the aim of this research. Our decision about which compounds to synthesis was aided by docking studies. Using data from the protein databank and refinement from BIOVIA discovery, the protein structure of AGF183 (PDB5IZQ). It was subjected to molecular docking investigations using PyRx 0.8 Autodock Vina software. following the creation of a novel sequence of thiophene-2,5-carbohydrazide. Final chemicals such as thiophene-2,5-carbohydrazide derivatives (G1 and G2) are produced via the Japp Klinegmann process. This reaction makes it possible to produce Schiff bases without any problems. Diethylthiophene-2,5-dicarboxylate was reacted with an aromatic diazonium salt to create the final products. When compared to the reference drug imatinib, the synthesized compounds exhibited the strongest anticancer effect. The study conducted on MCF-7 cell line demonstrated that compounds G1 and G2 demonstrated the most potent anticancer effect. Compared to the reference value of imatinib, which is 52.77 µg/ml and has G1 and G2 docking scores of -8.8, -8.6, and the standard medication methotrexate (-11.87 kcal/mol), their IC50 values were 46.52 µg/ml and 50 µg/ml. On base of characterization results above show that it Japp Klinegmann Synthesis method is useful for synthesis of thiophene hydrazone derivatives and its findings imply that the MCF-7 cells, which are utilized to potential treatment for human breast cancer.

Biomedical applications of terbium oxide nanoparticles by Couroupita guianensis aubl leaves extract: A greener approach

Couroupita guianensis aubl (CGA) is a plant known for its therapeutic characteristics and extensively used in biomedicine. This paper presents a method for synthesizing terbium oxide (Tb2O3) nanoparticles (NPs) utilizing the leaves extract of CGA which is sustainable and environmentally friendly. The practical synthesis of Tb2O3 NPs was validated using UV–vis analysis, revealing a prominent peak at 246 nm and the calculated band gap value of 3.02 eV. The existence of numerous functional groups and molecular bonding interactions in the Tb2O3 NPs was confirmed using FTIR spectrum analysis. In addition, the XRD examination confirmed that the nanoparticles had a crystalline structure with dimensions of 27.3 nm. The TEM imaging revealed the particle size of around 5.63 nm. The manufactured Tb2O3 NPs were analysed for anticancer capabilities against human MCF-7 cancer cell lines. Overall, our study emphasizes the ability of green-produced Tb2O3 NPs to be versatile agents with antidiabetic, antioxidant, and anticancer effects. These nanoparticles are potentially used in biomedical applications, providing long-lasting solutions to various health-related problems.

Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: In Vitro and In Vivo Studies Including Patient-Derived Organoids.

Precedential evidence ascertaining the overexpression of LSD1 and HDACs in colorectal cancer spurred us to design a series of dual LSD1-HDAC inhibitors. Capitalizing on the modular nature of the three-component HDAC inhibitory model, tranylcypromine as a surface recognition motif was appended to zinc-binding motifs via diverse linkers. A compendium of hydroxamic acids was generated and evaluated for in vitro cytotoxicity against HCT-116 cells (human colorectal cancer cell lines). The most potent cell growth inhibitor 2 (GI50 = 0.495 μMm HCT-116 cells) shows promising anticancer effects by reducing colony formation and inducing cell cycle arrest in HCT-116 cells. It exhibits preferential inhibition of HDAC6, along with potent inhibition of LSD1 compared to standard inhibitors. Moreover, Compound 2 upregulates acetyl-tubulin, acetyl-histone H3, and H3K4me2, indicative of LSD1 and HDAC inhibition. In vivo, it demonstrates significant antitumor activity against colorectal cancer, better than irinotecan, and effectively inhibits growth in patient-derived CRC organoids.

Marine Bioactives in Cancer Prevention and Treatment

The twice high incidence risk of cancer in men was the reason for over a million new cases and deaths recorded globally in 2018. The two most frequent cancer-related fatalities are lung and breast cancer. Novel therapies have been made possible by developments in immunotherapy, biology, and pharmaceutical design. Novel cancer prevention and therapy elements are being made possible by technological advancements and studies on marine natural resources. The creation of innovative anticancer medications is utilizing marine-derived natural products (MNPs). Biologically active polyketides, high molecular weight organic sugars, terpenes, bioengineered alkaloids, and marine animal peptides are some examples of these MNPs. Anticancer drugs are also developed with the help of plants, animals, invertebrates, and microbes found on land. The National Cancer Institute is exploring the potential of nutrition and food in cancer prevention despite the absence of preclinical and clinical data. Marine organisms contain bioactive compounds that have potential anticancer effects. Polyphenols, polysaccharides, and alkaloids are some of the active components found in marine species. Polyphenols, found in edible seaweeds like Palmaria palmata, can lower cancer cell division and proliferation, while polysaccharides trigger the innate immune system, causing apoptosis in pancreatic islet cancer and human leukemia cells. Alkaloids, derived from marine sources, can inhibit cancer cell development. Peptides, found in various plant species, have shown cytotoxic effects on several human cell lines, including pancreatic, breast, lung, and bladder cancers. Marine drug approval faces challenges like the possibility of a resurgence of different metabolites due to environmental conditions and limited lead compound availability.

MiR‑25‑3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function.

Accumulating evidence indicates that the dysregulation of microRNAs (miRNAs or miRs), is associated with human malignancies and suggests a casual role of miRNAs in tumor initiation and progression. Even though it has been discovered that a number of miRNAs play significant parts in the development of colorectal cancer (CRC), it is crucial to comprehend the regulatory functions that other miRNAs play in CRC. Based on GSE183437 and GSE156719 microarray data that were obtained from Gene Expression Omnibus database, candidate miRNAs were researched. The oncogenic effects of miR‑25‑3p in different malignancies have led to its selection for additional investigation in the present study. The expression of miR‑25‑3p was verified by reverse transcription‑quantitative PCR, and its correlation with clinicopathological characteristics in patients with CRC was then investigated. In vitro assays were conducted to investigate the influence of miR‑25‑3p on the proliferative and apoptotic behaviors of HCT116 and Caco‑2 cells. The present data revealed that miR‑25‑3p exhibited one of the most significant upregulations in CRC tissues and cell lines. The expression levels of miR‑25‑3p were found to be intimately correlated with tumor size, distant metastasis, tumor‑node‑metastasis stage, and shorter overall survival rate. In terms of functionality, the downregulation of miR‑25‑3p led to the inhibition of cellular proliferation and the enhancement of apoptosis in both HCT116 and Caco‑2 cell lines. The critical tumor suppressor F‑box and WD repeat containing domain 7 (FBXW7) was identified as a direct molecular target for miR‑25‑3p, with an inverse relationship observed between the two in neoplastic tissues. Subsequent studies demonstrated that the tumor suppressive effects of miR‑25‑3p inhibitor were effectively negated by the silencing of FBXW7. Moreover, the ability of FBXW7 to inhibit the expression of several oncogenes was deemed essential for countering the anticancer effects mediated by miR‑25‑3p downregulation. These findings posit miR‑25‑3p as a promising therapeutic target and prognostic indicator for CRC.

Enhanced anti-cancer efficacy of arginine deaminase expressed by tumor-seeking Salmonella Gallinarum.

Amino acid deprivation, particularly of nonessential amino acids that can be synthesized by normal cells but not by cancer cells with specific defects in the biosynthesis pathway, has emerged as a potential strategy in cancer therapeutics. In normal cells, arginine is synthesized from citrulline in two steps via two enzymes: argininosuccinate synthetase (ASS1) and argininosuccinate lyase. Several cancer cells exhibit arginine auxotrophy due to the loss or down-regulation of ASS1. These cells undergo starvation-induced cell death in the presence of arginine-degrading enzymes such as arginine deaminase (ADI). Thus, ADI has emerged as a potential therapeutic in cancer therapy. However, the use of ADI has two major disadvantages: ADI of bacterial origin is strongly antigenic in mammals, and ADI has a short circulation half-life (∼5 h). In this study, we engineered tumor-targeting Salmonella Gallinarum to express and secrete ADI and deployed this strain into mice implanted with ASS1-defective mouse colorectal cancer (CT26) through an intravenous route. A notable antitumor effect was observed, suggesting that the disadvantages were overcome as ADI was expressed constitutively by tumor-targeting bacteria. A combination with chloroquine, which inhibits the induction of autophagy, further enhanced the effect. Anti-cancer effect of Salmonella Gallinarum expressing an arginine deiminase (ADI) on arginine-dependent tumors in situ.

Milk-Derived Exosomes: Innovative Nanocarriers for Enhanced Anticancer Drug Delivery

This in-depth review examines the recently emerging field of using exosomes from milk as anticancer medication nanocarriers. It gives a summary of the most current developments, difficulties, and opportunities in this cutting-edge therapeutic strategy. Exosomes are found in many different body fluids and are considered a promising option for precision medicine due to their biocompatibility and innate cell-targeting abilities. These extracellular vesicles are nanoscale. The review commences with a comprehensive synopsis of the composition and biogenesis of exosomes derived from milk, highlighting their distinct membrane properties and capacity to transport cargo. Interestingly, these naturally occurring nanocarriers hold a variety of bioactive substances that can be precisely delivered as anticancer medications. These substances include proteins, lipids, and nucleic acids. Because dietary(poly) phenols are rapidly metabolized, their ability to prevent cancer is limited. Extracellular vesicles called exosomes may shield polyphenols from metabolism. Our objective was to evaluate the anticancer effects of free curcumin and resveratrol in breast cancer cell lines compared to their encapsulation in extracellular matrix derived from milk. Breast tissue was disposed of kinetically using rats. Curcumin and resveratrol were assessed using UPLC-QTOF-MS and GV-MS, respectively. Dietary polyphenols have a limited capacity to prevent cancer due to their rapid metabolism. Extracellular vesicles called exosomes may shield polyphenols from metabolism. Our goal was to assess in breast tissue. UPLC-QTOF-MS and GV-MS were used to evaluate curcumin and resveratrol, respectively. Curcumin and Resveratrol anticancer activity and bioavailability were improved by milk extracellular urea, which served as Trojan horses to get around the ABC-mediated chemoresistance of cancer cells. Exosomes derived from milk are being studied for their potential as carriers of therapeutic and diagnostic agents, emphasizing the potential benefits of personalized and precision medicine approaches to cancer treatment. The review also covers the challenges that the clinical translation of milk-derived exosome-based drug delivery systems currently faces, including scalability, standardization and safety profiles. The article's conclusion presents an optimistic view of how milk-derived exosomes will develop in the future in terms of anticancer medication delivery. The review highlights the revolutionary potential of using milk-derived exosomes, nature's nanocarriers, to advance the field toward more precise and effective cancer treatments, anticipating future advancements and emerging trends.

Synthesis, characterization and anticancer, antibacterial activities of pentacyclic triterpenoid glycoside derivatives

As a kind of glycoside, pentacyclic triterpenoid saponins have good biological activities, such as anticancer, antibacterial, antiviral and hypoglycemic effects [1]. In this paper, twenty-four pentacyclic triterpenoid derivatives, including twelve monosaccharide derivatives, were designed and synthesized. The anticancer effect and antibacterial activities of all compounds were evaluated. It is noteworthy that compound UA-2b has the strongest inhibitory effect on the growth of A549, Hela and HepG2 cancer cells (IC50 = 5.37 ± 0.22 µM, 5.82 ± 0.25 µM and 5.47 ± 0.06 µM, respectively). Compounds OA-2b, OA-6a, OA-6b, UA-2b and UA-6a have the best activity against Escherichia coli 1924 (MIC = 16 μg/ml).