Types Of Cancer Cells Research Articles

Apium graveolens leaf ethanolic extract triggers apoptosis in human tongue cancer cells via caspase-3 and poly(ADP-ribose) polymerase pathways: An in vitro study

Recent advances in cancer treatment have focused on developing alternative therapies with reduced adverse effects. Chemoprevention using natural products derived from plants has gained significant attention. Apium graveolens has demonstrated anticancer properties against various cancer cell types, suggesting its potential efficacy against tongue cancer cells. The aim of this study was to evaluate the cytotoxic effects and mechanisms of action of Apium graveolens leaf ethanolic extract (AGLEE) on the HSC-3 tongue cancer cell line. The leaves were processed and extracted with 70% ethanol to obtain an ethanolic extract. HSC-3 cells were cultured, subjected to starvation, and pre-treated with or without Z-DEVD-FMK, a caspase-3 inhibitor. Subsequently, the cells were treated with or without doxorubicin or varying concentrations of AGLEE. To assess cell viability and apoptosis, MTT and sub-G1 assays were performed. Additionally, treated HSC-3 cells were collected, lysed, and analyzed for levels of cleaved-caspase-3 and cleaved-poly (ADP-ribose) polymerase (cleaved-PARP) using ELISA. The inhibitory concentration (IC50) value of AGLEE for reducing viable HSC-3 cells was determined to be 48.29 μg/mL. AGLEE significantly decreased HSC-3 cell viability and increased the percentage of apoptotic cells. It exhibited a concentration-dependent reduction in cell viability and an increase in apoptosis. Furthermore, the extract elevated the levels of cleaved-caspase-3 and cleaved-PARP in HSC-3 cells. Pre-treatment with Z-DEVD-FMK reduced the levels of cleaved-caspase-3 and cleaved-PARP induced by AGLEE. Taken together, AGLEE could be proposed as a potential natural therapeutic agent by inducing apoptosis through the caspase-3/PARP pathway in tongue cancer cells.

Microalgae: A Treasure Trove of Anticancer Nutraceuticals and Promising Therapeutic Mechanisms

With cancer remaining a global health concern, the need for new and effective preventive and treatment methods is paramount. Microalgae have emerged as a potential source of anticancer nutraceuticals. Our research indicates that substances produced from microalgae, such as carotenoids, polyunsaturated fatty acids, phycocyanin, and polysaccharides, have shown anticancer effects in both laboratory and human investigations. Carotenoids, including astaxanthin, have shown the ability to hinder the development of tumors and trigger programmed cell death (apoptosis) in several types of cancer cells. Moreover, studies have shown that phycocyanin, a blue pigment present in some species of microalgae, has properties that help reduce inflammation and combat cancer. Potential future research directions include expanding the scope of the study to encompass a diverse range of microalgae species, identifying other compounds with anticancer properties, and investigating the mechanisms by which chemicals derived from microalgae function in the treatment and prevention of cancer. Moreover, it is important to establish scalable and sustainable procedures for the industrial production of compounds derived from microalgae. In conclusion, our evaluation reveals that microalgae have enormous potential as a source of anticancer nutraceuticals, containing a variety of bioactive substances that could eventually lead to the development of novel and effective cancer prevention and treatment methods. To realize the maximum potential of chemicals derived from microalgae, it is necessary to develop a sustainable and environmentally benign industry and to continue research in this area.

Evaluation of Stability and In vitro Anti-Cancer Activity of Dihydroquercetin Nanoemulsion

Background: Dihydroquercetin (DHQ), also known as taxifolin, is a flavonoid commonly found in many plants. Dihydroquercetin has been documented to have powerful antioxidant activity and many beneficial properties for human health, especially its ability to inhibit certain types of cancer cells. However, its low solubility and bioavailability are major obstacles to biomedical applications. Moreover, DHQ is chemically unstable and quickly degrades when exposed to alkaline conditions. Objective: In the present study, a DHQ nanoemulsion formulation was prepared by Self Nano- Emulsifying Drug Delivery System (SNEDDS) technique to overcome the above disadvantages. Methods: The obtained nanoemulsion system was evaluated for its micro-properties, stability, and in vitro cytotoxic activity against some cancer cells using tetrazolium dyes (MTS assay). Results: Measurement results showed that the DHQ nanoemulsion was successfully synthesized with typical mean droplet sizes from 9 to 11 nm, and revealed excellent stability over time. Dihydroquercetin in nanoemulsion form is more stable than the non-encapsulated form, as evidenced by the maintenance of droplet size in the nanometer range when dispersed in aqueous solution for up to 48 hours. This stability is particularly pronounced in both acidic and neutral environments. In vitro experiments on cytotoxic activities against A549, Hela, and HepG2 cancer cell lines indicated that the prepared DHQ nanoemulsion effectively inhibited the growth of all these cell lines with IC50 values (μg/mL) of 8.0, 20.4, and 29.5 respectively. Conclusion: From the detailed results above, it is evident that the solubility and bioavailability of DHQ can be improved by creating its nanostructure in the form of nanoemulsions. Furthermore, the nano form of DHQ carried within stable nanoemulsions exhibited better performance in inhibiting cancer cells compared to free DHQ. Therefore, further research is required to explore the development of cancer therapeutics utilizing nano DHQ emulsions.

Colony-Forming and Cell Viability Assay to Assess Nanotoxicity of Maleic Acid and N-vinyl Caprolactam-Based Nanoarchitectures

Abstract Organo-montmorillonite (Org-MMT) is a widely used silicate in polymer nanotechnology, enhancing the durability of nanocomposites by improving polymer strength and thermal stability. This study evaluates the anticancer effects of poly(maleic anhydride-alt-N-vinyl caprolactam) [poly(MA-alt-VCL)]-Org-MMT nanocomposites synthesized with varying clay concentrations. The cytotoxicity of Org-MMT, poly(MA-alt-VCL), and their nanocomposites were tested on HeLa (cervical carcinoma), A549 (lung cancer), and HDF (human dermal fibroblast) cells using MTT and colony formation assays. Our results indicate that cell viability is significantly inhibited in both cancer cell types with an IC50 value of 2 mg/mL especially in A549 cells, while 10 mg/mL in HDF cells. Nanocomposites significantly inhibited colony formation in both cancer cell lines, particularly in the HeLa cell line. The data indicated an inverse correlation between clay content in the copolymer complex and cell viability. The copolymer complex without clay had no negative impact on the cells. These findings suggest organo-clay nanocomposites as promising candidates for anticancer drug research.

Gene-knockdown Methods for Silencing Nuclear-localized Insulin Receptors in Lung Adenocarcinoma Cells: A Bioinformatics Approach.

Lung adenocarcinoma, the predominant subtype of lung cancer, presents a significant challenge to public health due to its notably low five-year survival rate. Recent epidemiological data highlights a concerning trend: patients with pulmonary adenocarcinoma and comorbid diabetes exhibit substantially elevated mortality rates compared to those without diabetes, suggesting a potential link between hyperinsulinemia in diabetic individuals and accelerated progression of pulmonary adenocarcinoma. Insulin Receptor (IR) is a tyrosine-protein kinase on the cell surface, and its over-expression is considered the pathological hallmark of hyperinsulinemia in various cancer cell types. Research indicates that IR can translocate to the nucleus of lung adenocarcinoma cells to promote their proliferation, but its precise molecular targets remain unclear. This study aims to silence IRs in lung adenocarcinoma cells and identify key genes within the ERK pathway that may serve as potential molecular targets for intervention. Gene expression data from lung adenocarcinoma and para cancer tissues were retrieved from the Gene Expression Omnibus (GEO) database and assessed through "pheatmap", GO annotation, KEGG analysis, R calculations, Cytoscape mapping, and Hub gene screening. Significant genes were visualized using the ggplot2 tool to compare expression patterns between the two groups. Additionally, survival analysis was performed using the R "survminer" and "survival" packages, along with the R "pathview" package for pathway visualization. Marker genes were identified and linked to relevant signaling pathways. Validation was conducted utilizing real-time quantitative polymerase chain reaction and immunoblotting assays in an A549 lung cancer cell model to determine the roles of these marker genes in associated signaling cascades. The study examined 58 lung adenocarcinoma samples and paired para-neoplastic tissues. Analysis of the GSE32863 dataset from GEO revealed 1040 differentially expressed genes, with 421 up-regulated and 619 down-regulated. Visualization of these differences identified 172 significant alterations, comprising 141 up-regulated and 31 down-regulated genes. Functional enrichment analysis using Gene Ontology (GO) revealed 56 molecular functions, 77 cellular components, and 816 biological processes. KEGG analysis identified 17 strongly enriched functions, including cytokine interactions and tumor necrosis factor signaling. Moreover, the ERK signaling pathway was associated with four Hub genes (FGFR4, ANGPT1, TEK, and IL1B) in cellular biological processes. Further validation demonstrated a positive correlation between IL-1B expression in the ERK signaling pathway and lung cancer through real-time fluorescence quantitative enzyme-linked reaction with immunoblotting assays. In IR-silenced lung adenocarcinoma, the expression of the IL-1B gene exhibited a positive correlation with the ERK signaling pathway.

Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-Naphthoquinone Hybrids.

Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science. This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC). Given the significance of both naphthoquinones and coumarins as essential pharmacophores/ privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma. By several in vitro, in silico, and in vivo approaches, we demonstrated that compound 6e was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound 6e was non-hemolytic and tolerated in vivo at 50 mg/kg with an LD50 of 62.5 mg/kg. Furthermore, compound 6e did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, 6e had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity in vitro. We assert that compound 6e shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types.

Novel methods for the detection of glutathione by surface-enhanced Raman scattering: A perspective review.

Detection of biomolecules, Glutathione (GSH) in particular, is important because it helps assess antioxidant capacity, cellular protection, detoxification processes, and potential disease associations. Monitoring glutathione levels can provide valuable information about overall health and well-being. Many medical disorders have been connected to glutathione levels. Higher glutathione levels have been seen in several cancer cell types, which may increase their resistance to radiation and chemotherapy. Glutathione levels can be measured through various methods, such as colorimetric assays and fluorescent probes. However, surface-enhanced Raman scattering (SERS) has been known as an efficient and selective technique for biomolecule detection. Here in this perspective review, we have reported two distinctive methods based on SERS technique in detection of GSH; heat-induced method and reversed reporting agent method. Several variables that can impact the detection scheme were elaborated in the "heat-induced method," including pretreatment, nanoparticle reduction time, the process temperature, the pH of the colloidal solution, the concentration of citrate buffer, and the concentration of participating nanoparticles. To choose the best reporting agent for a reverse reporting scheme using SERS approaches, several reporting agents were examined in the second method. In order to grasp the situation at hand, biomolecule detection-specifically, GSH detection schemes-was briefly discussed. SERS spectroscopy and its associated terminology were then covered followed by the perspective and outlook of GSH detection at the end. To meet the demands of real-time applications in everyday life and to enhance SERS methods for biomolecule detection-in particular, GSH detection-such a thorough investigation is unavoidable.

Investigating the effect of femtosecond laser pulses on noscapine and curcumin cellular uptake and improving drug delivery in gastric cancer cells.

The MKN45cell line, a type of gastric cancer cell, exhibits resistance to chemotherapy agents through various mechanisms. Curcumin and noscapine, two plant-derived anticancer compounds, exhibit selective cytotoxicity towards cancer cells. However, their bioavailability is poor both in vitro and in vivo. In this study, we used femtosecond laser pulses in the near-infrared region (central wavelength of 1040nm) with a pulse duration of 200fs, a beam diameter of 4mm, and different pulse energies and average powers to perforate the plasma membrane. We standardized the necessary conditions while minimizing cellular necrosis. MKN45 cells were treated with 25-200μM curcumin and noscapine for 24h after irradiation with an optimized femtosecond laser exposure (40mW, 40sec) or without irradiation. The MTT cell viability assay revealed that pre-treatment with femtosecond (fs) laser pulses significantly increased cellular sensitivity to the treatment. Overall, the findings suggest that fs laser pulses irradiation enhance the bioavailability of both curcumin and noscapine. The combined treatment of femtosecond laser pulses and drugs can improve the drug's efficacy and the overall treatment outcome.

Key Magnetized Exosomes for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Cell Types in Mice Model [Letter

Key Magnetized Exosomes for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Cell Types in Mice Model [Letter

Novel benzoylurea derivative decreases TRPM7 channel function and inhibits cancer cells migration

ABSTRACT The transient receptor potential melastatin 7 channel (TRPM7) is a nonselective cation channel highly expressed in some human cancer tissues. TRPM7 is involved in the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cancer cells. Modulation of TRPM7 could be a promising therapeutic strategy for treating cancer; however, efficient and selective pharmacological TRPM7 modulators are lacking. In this study we investigated N- [4- (4, 6-dimethyl- 2-pyrimidinyloxy) − 3- methylphenyl] -N’ - [2 -(dimethylamino)] benzoylurea (SUD), a newly synthesized benzoylurea derivative, for its effects on cancer cell migration and EMT and on functional expression of TRPM7. Our previous studies showed that SUD induces cell cycle arrest and apoptosis of MCF-7 and BGC-823 cells (human breast cancer and gastric cancer cell lines, respectively). Here, we show that SUD significantly decreased the migration of both types of cancer cells. Moreover, SUD decreased vimentin expression and increased E-cadherin expression in both cell types, indicating that EMT is also decreased by SUD. Importantly, SUD potentially reduced the TRPM7-like current in a concentration-dependent manner and decreased TRPM7 expression through the PI3K/Akt signaling pathway. Finally, molecular docking simulations were used to investigate potential SUD binding sites on TRPM7. In summary, our research demonstrated that SUD is an effective TRPM7 inhibitor and a potential agent to suppress the metastasis of breast and gastric cancer by inhibiting TRPM7 expression and function.

Immune Cell Profiling Reveals a Common Pattern in Premetastatic Niche Formation Across Various Cancer Types

ABSTRACTBackgroundMetastasis is the major cause of cancer‐related mortality. The premetastatic niche is a promising target for its prevention. However, the generality and cellular dynamics in premetastatic niche formation have remained unclear.AimsThis study aimed to elucidate the generality and cellular dynamics in premetastatic niche formation.Materials and MethodsWe performed comprehensive flow cytometric analysis of lung and peripheral immune cells at three time points (early premetastatic, late premetastatic, and micrometastatic phases) for mice with subcutaneous implants of three types of cancer cells (breast cancer, lung cancer, or melanoma cells). The immuno‐cell profiles were then used to predict the metastatic phase by machine learning.ResultsWe found a common pattern of changes in both lung and peripheral immune cell profiles across the three cancer types, including a decrease in the proportion of eosinophils in the early premetastatic phase, an increase in that of regulatory T cells in the late premetastatic phase, and an increase in that of polymorphonuclear myeloid‐derived suppressor cells and a decrease in that of B cells in the micrometastatic phase. Machine learning using immune cell profiles could predict the metastatic phase with approximately 75% accuracy.DiscussionValidation of our findings in humans will require data on the presence or absence of micrometastases in patients and the accumulation of comprehensive and temporal information on immune cells. In addition, blood proteins, extracellular vesicles, DNA, RNA, or metabolites may be useful for more accurate prediction.ConclusionThe discovery of generalities in premetastatic niche formation allow prediction of metastatic phase and provide a basis for the development of methods for early detection and prevention of cancer metastasis in a cancer type‐independent manner.

Discovery of a Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads.

Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein, we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for the rapid identification of microbial natural products with both novel structures and potent activities. Additionally, we demonstrate the use of microcrystal electron diffraction (MicroED) for direct structure elucidation of lead compounds from partially purified mixtures. Using this strategy to screen geographically and phylogenetically diverse microbial metabolites against pseudomyxoma peritonei, a rare and severe cancer, we discovered a new class of leads, aspercyclicins. The aspercyclicins feature an unprecedented tightly packed polycyclic polyketide scaffold that comprises continuous fused, bridged, and spiro rings. The biogenesis of aspercyclicins involves two distinct biosynthetic pathways, leading to formation of chimeric compounds that cannot be predicted by bottom-up approaches mining natural product biosynthetic genes. With comparable potency to some clinically used anticancer drugs, aspercyclicins are active against multiple cancer cell types by inducing immunogenic cell death (ICD), including the release of damage-associated molecular patterns and subsequent phagocytosis of cancer cells. The broad-spectrum ICD-inducing activity of aspercyclicins, combined with their low toxicity to normal cells, represents a new class of potential cancer immunogenic chemotherapeutics and, particularly, the first drug lead for pseudomyxoma peritonei treatment.

A review of strategies for targeting and killing cancer stem cells based on their origin characterization

The discovery of cancer stem cells (CSCs) is of great significance in the field of cancer biology research. They are tumourigenic cancer cells with similar properties to normal stem cells, especially in terms of their ability to form various cancer cells types found in tumour samples, which resembles the pluripotency of normal stem cells. Unlike non-tumorigenic cancer cells, CSCs are able to generate tumors through stem cell-like processes of self-renewal and differentiation. Hypothetically, CSCs cause the cancer cells to persist in patients, leading to relapse by forming new tumours through this property. Therefore, development of specific therapies targeted at CSCs presents a new strategy to improve the survival and quality of life of cancer patients by potentially preventing cancer recurrance after remission and metastasis in early cancer patients. This research paper compares cancer stem cells and normal stem cells to explore their possible connections and discusses the possibility of modifying CSCs into a differentiated state to reduce its tumorigenicity.

Anticancer Ribosomally Synthesized and Post-Translationally Modified Peptides from Plants: Structures, Therapeutic Potential, and Future Directions.

Cancer remains a significant medical challenge, necessitating the discovery of novel therapeutic agents. Ribosomally synthesized and post-translationally modified peptides (RiPPs) from plants have emerged as a promising source of anticancer compounds, offering unique structural diversity and potent biological activity. This review identifies and discusses cytotoxic RiPPs across various plant families, focusing on their absolute chemical structures and reported cytotoxic activities against cancer cell lines. Notably, plant-derived RiPPs such as rubipodanin A and mallotumides A-C demonstrated low nanomolar IC50 values against multiple cancer cell types, highlighting their therapeutic potential. By integrating traditional ethnobotanical knowledge with modern genomic and bioinformatic approaches, this study underscores the importance of plant RiPPs as a resource for developing innovative cancer treatments. These findings pave the way for further exploration of plant RiPPs, emphasizing their role in addressing the ongoing challenges in oncology and enhancing the repertoire of effective anticancer therapies.

Exploring Marine Compounds for Inhibition of the BRAF V600E Mutation in Lung Cancer: A High Throughput Virtual Screening Approach

The BRAF V600E mutation is present in a variety of cancer cell types, including lung cancer, which is a leading cause of cancer-related death globally. Drugs like Dabrafenib and Vermaifenib were specifically used in targeted therapy for patients with BRAF V600E mutation. Drug resistance is typical, though, and more study is required to improve therapeutic strategies for this subset of lung cancer. Recently, marine natural compounds have emerged as a resource for the development of novel cancer therapeutics. In this study, we used virtual screening of marine compounds to find potential therapeutic candidates for NSCLC patients with the BRAF V600E mutation. We developed a receptor-based pharmacophore model and screened a library of 31,561 compounds from the Comprehensive Marine Natural Products Database (CMNPD) using a virtual screening protocol that was constructed and validated. Molecular docking was performed using CDOCKER to investigate potential inhibitors and ADMET for their toxicity and other properties. Seven compounds exhibited higher efficacy than the experimentally verified compound of BRAF mutation. A molecular dynamics simulation was performed to confirm the stability of the docked compounds and compare them with the experimentally verified compound. Our study identified, out of seven, the CMNPD7700 compound as a potential drug candidate for further development due to its high, effectiveness and molecular stability.

Demographics and Histopathological Characteristics of Lung Cancer Patients in Cirebon District, Indonesia (2021-2023)

Background: Based on the Global Burden of Cancer Study (GLOBOCAN) in 2020, In the world, lung cancer is the first cause of death. In Indonesia, lung cancer is the third highest. Lung cancer is classified into two cell types: Small Cell Lung Cancer and Non-Small Cell Lung Cancer. There are two types of Non-Small Cell Lung Cancer: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Aims: To determine the demographics and histopathological characteristics of lung cancer patients in Cirebon District (2021-2023). Methods: This research employed a descriptive observational method. The data were collected from general hospitals’ medical records of lung cancer patients at RSUD Waled Cirebon and RSUD Arjawinangun in 2021-2023 using the total sampling technique. There were 69 respondents met the inclusion criteria for this recent study. Results: In this study, there were 68.1% of patients aged from 46 to 70 years, and the majority were male (66.7%). The most common cancer cell type was adenocarcinoma (69.6%). Most patients did not have information regarding occupational data (68.1%), smoking history (98.6%), family history (98.6%), and staging (89.9%) included in their medical records. Conclusion: The analysis showed that most lung cancer patients are aged 46-70 years and male incidences in lung cancer patients were higher. The most common type of histopathological is adenocarcinoma. Related to occupational data, smoking history, family history, and staging could not be concluded because they were not included in the medical record. Received: 25 September 2024 | Reviewed: 19 October 2024 | Revised: 30 November 2024 | Accepted: 12 December 2024.

Anticancer effects of aloe-emodin from Rheum undulatum L. through activation of the p53 pathway in human prostate cancer cells

Aloe-emodin, an anthraquinone compound naturally derived from Rheum undulatum L., has gained extensive research attention owing to its various pharmacological effects, including its potential as an anticancer, antivirus, anti-inflammatory, antibacterial, and anti-parasitic agent. It has demonstrated notable inhibitory effects against various types of cancer and cancer cells. Prostate cancer is among the most commonly identified cancers globally and remains a leading cause of cancer-associated deaths in men, often presenting challenges in early detection due to its asymptomatic nature during initial stages. The aim of present study was to determine the biological activity of aloe-emodin obtained from Rheum undulatum L. involving activation of the p53-dependent pathway in certain human prostate cancer cell lines. We explored the mechanisms underlying the anticancer effects of aloe-emodin using LNCaP cells, which include p53-wild type and phosphatase and tensin homolog-deficient mutated genes, a widely studied model in genomic research. Aloe-emodin induced apoptosis in LNCaP cells through several mechanisms, including upregulation of the cleavage of caspase-8 (a cross-linked promoter of cell death signals), phosphorylation of p53 at serine 15, DNA fragmentation, cleavage of poly [ADP-ribose] polymerase, and promotion of cell death. These findings strongly indicated that aloe-emodin's anticancer properties in human prostate cancer involve the activation of p53-induced cellular senescence. Conclusively, the findings of this study imply that aloe-emodin extracted from Rheum undulatum L. is a potential therapeutic compound for adjuvant chemotherapy that induces apoptosis and pyroptosis, an innate immune response, in preventing the progression of precancerous lesions in patients with prostate cancer.

Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis.

Background/Objectives: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (Betula pendula) outer bark (TTs) and to evaluate their potential as anticancer agents in vitro, using Melanoma B16-F10 and Walker carcinoma cells. Methods: Appropriate solvents were selected for efficient TTs extraction, and original recipes were used to obtain Pegylated liposomes and nanolipid complexes with entrapped TTs, comparative to pure standards (betulinic acid and doxorubicin) in similar conditions. The composition, morphology, and sizes of all nanoformulations were checked by high-performance liquid chromatography/mass spectrometry, Transmission Electronic Microscopy, and Diffraction Light Scattering. The entrapment efficiency and its impact on cell viability, cell cycle arrest, and apoptosis by flow cytometry was also measured on both cancer cell lines. Conclusions: The standardized TTs, including betulin, lupeol, and betulinic acid, showed good stability and superior activity compared to pure betulinic acid. According to experimental data, TTs showed good entrapment in liposomal and NLC nanoformulations, both delivery systems including natural, biodegradable ingredients and enhanced bioavailability. The apoptosis and necrosis effects were more pronounced for TTs liposomal formulations in both types of cancer cells, with lower cytotoxicity compared to Doxorubicin, and can be correlated with their increased bioavailability.

Exploring the promising therapeutic benefits of iodine and radioiodine in breast cancer cell lines.

Iodine has an anti-proliferative effect on cancer cells; however, its effects have not been explored adequately. The aim of this study was to evaluate the therapeutic potential of iodine and radioiodine by assessing their effects on the viability of various breast cancer cell lines: MCF7, SKBR3, and MDA-MB231. The viability of cells was measured in treated cells exposed to six doses of iodine (5, 10, 20, 40, 60, 80 µM) and two doses of radioiodine (3.7 × 104 and 3.7 × 105 Bq). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and modified clonogenic assays were used to assess cell viability. Exposure to 80 µM of iodine significantly reduced the viability of all cell types. The cells were then exposed to a 50% inhibitory concentration (IC50) dose. When the cells were exposed to the IC50 dose of iodine, the MCF7 cell viability was reduced by 42.6 ± 0.14% (IC50 dose 12.88 µM), 40.2 ± 0.08% for SKBR3 (IC50 dose 11.03 µM) and 47.0 ± 0.02% for MDA-MB231 (IC50 dose 14.09 µM). All cells were also exposed to 3.7 × 104 Bq and 3.7 × 105 Bq radioiodine. Both doses significantly reduced the cell viability of MCF7 and SKBR3 cells compared to the unexposed control cells (all had p < 0.05), while MDA-MB231 cell viability only reduced significantly after 3.7 × 105 Bq of radioiodine exposure compared to the unexposed control cells (p < 0.05). This study highlighted that iodine had a toxic effect on breast cancer cells, and radioiodine enhanced the toxicity to breast cancer cells. The types of cancer cells and doses of iodine and radioiodine influenced the effect. These findings suggest that iodine and radioiodine hold promise as therapeutic agents for breast cancer, similar to their established use in thyroid disease treatment. However, further in vivo studies are important to provide more evidence.

Sea Hare Hydrolysate Reduces PD-L1 Levels in Cancer Cells and Mitigates Rheumatoid Arthritis Ina Collagen-Induced Arthritis Mouse Model.

Our previous study highlighted the anticancer potential of sea hare hydrolysate (SHH), particularly its role in regulating macrophage polarization and inducing pyroptotic death in lung cancer cells through the inhibition of signal transducer and activator of transcription 3 (STAT3). These findings prompted us to investigate additional features of immune-oncology (I-O) agents or adjuvants, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition and their association with rheumatoid arthritis (RA) risk, to explore the potential of SHH as an I-O agent or adjuvant. In this study, we investigated the effects of SHH on PD-L1 levels in various cancer cell types and assessed its effectiveness in treating RA, a common side effect of I-O agents. Our results showed a marked reduction in PD-L1 levels in multiple cancer cell lines and decreased PD-1 and PD-L1 levels in tumor-associated macrophages. In a mouse model with collagen-induced arthritis (CIA), SHH exhibited anti-inflammatory effects comparable to methotrexate (MTX), a first-line treatment for RA. Both the SHH and MTX groups had significantly lower arthritis scores and paw thickness compared to the CIA group. Additionally, SHH or MTX treatment effectively reduced elevated levels of anticollagen type II (CII) antibodies and proinflammatory cytokines (IL-1β, IL-6, and TNF-α). Histopathological analysis revealed that SHH and MTX treatments notably mitigated arthritic inflammation, synovial hyperplasia, and loss of articular cartilage and bone. Micro-CT scans showed reduced articular destruction in the SHH and MTX groups. These findings indicate that SHH treatment decreases PD-L1 levels in cancer cells and reduces the severity of CIA by exerting anti-inflammatory effects. Therefore, SHH holds promise as an I-O agent without side effects such as exacerbation of RA.