Untreated Cancer Cells Research Articles

MicroRNA-145 enhances lung cancer cell progression after exposure to lyophilized fertile hydatid cyst fluid of Echinococcus granulosus sensu stricto

There is increasing evidence that the secretory/excretory antigens of the larval stage of Echinococcus granulosus can induce both anticancer and oncogenic effects between parasite-derived metabolites and various cancer cells. The dual role of miR-145 as either a tumor suppressor or oncogene has already been reported in cancer. However, the mechanism by which miR-145 induces apoptosis in lung cancer cells treated with hydatid cyst fluid (HCF) remains unclear. The fertile HCF was obtained from sheep, purified and lyophilized. H1299 human lung cancer cells were then cultured into two groups: HCF-treated H1299 lung cancer cells and untreated H1299 cancer cells as control cells. Cell viability was assessed using MTT assay to evaluate the effects of HCF on the H1299 cells. Caspase-3 activity was assessed by fluorometric assay. In addition, mRNA expression levels of VGEF, vimentin, caspase-3, miRNA-145, Bax and Bcl-2 genes were quantified by real-time PCR. A scratch test was also performed to assess the effects of HCF on cell migration. The MTT assay revealed that the growth of H1299 cells increased when treated with 60 μg/mL of fertile HCF for 24 h. The fold change of caspase-3, miRNA-145, Bax/Bcl-2 ratio and caspase-3 activity was lower in HCF-treated H1299 cells compared to the control cell. The fold change in VGEF and vimentin gene expression was higher in the HCF-treated H1299 cells than in the control cell. The scratch test results showed that H1299 cell mobility increased 24 and 48 h after exposure to HCF. Our results suggest that the downregulation of miR-145 in HCF-treated H1299 cells may play a role as a possible oncogenic regulator of lung cancer growth. To confirm this assumption, further studies are required to evaluate the microRNA profile and effective oncogenes in vivo.

Effects of Vitamins E and D on Mechanical Properties of Breast Cancerous Cells

Background: Several investigations have demonstrated that vitamins can treat or prevent cancer by altering actin filaments and inhibiting cell migration and proliferation. Vitamins D and E are fat-soluble. This research aims to determine the short-term impact of vitamin D and E on the mechanical properties of breast cancer cells before comparing them with normal breast cells. Methods: Atomic force microscopy (AFM) was used to examine the deformation of MCF-10 normal breast cells, MCF-7 breast cancer cells, and MCF-7 breast cancer cells treated with 0.03 μM vitamin D and 16 μM vitamin E solutions. Young's modulus was calculated employing the Hertz model to determine cell stiffness. Results: The Young's modulus of vitamin D-treated cancer cells (585.8 Pa) was substantially similar to that of normal cells (455.6 Pa). Nevertheless, vitamin E treatment did not affect Young's modulus of cancer cells, which remained remarkably similar to that of untreated cancer cells (216.6 and 203.4 Pa, respectively). Conclusion: Unlike vitamin E, vitamin D enhances the stiffness of tumor cells and makes their mechanical properties similar to normal cells by interfering with actin filaments and cell skeletons, which may inhibit tumor cell migration. Based on these findings, vitamin D appears to be an effective drug for cancer treatment.

Enhanced anti-breast cancer activity of green synthesized selenium nanoparticles by PEGylation: induction of apoptosis and potential anticancer drug delivery system

Breast cancer is a disease associated with high morbidity and mortality rates worldwide. The potential use of biogenic nanoparticles as alternative anticancer agents has been immensely acknowledged in several studies, particularly selenium nanoparticles (SeNPs). Nanoparticles were synthesised using the aqueous extract of Moringa peregrine (MPM-SeNPs) and were PEGylated (PEG-MPM-SeNPs). MPM-SeNPs were characterised by chemical and physical techniques. The successful capping of MPM-SeNPs with PEG was confirmed by spectrophotometric measurements and via Fourier-transform infrared spectroscopy (FT-IR) analysis. Furthermore, the effect of PEGylation of MPM-SeNPs on enhancing their anti-breast cancer activity and as a drug delivery agent was evaluated. Therefore, the loading efficiency and release of DOX at different pH values were measured; the antiproliferative activity of PEG-MPM-SeNPs against the adenocarcinoma breast cancer cell line (MDA-MB-231) was evaluated and compared with that of biogenic MPM-SeNPs and DOX-conjugated PEG-MPM-SeNPs. PEG-MPM-SeNPs and DOX-PEG-MPM-SeNPs had reduced IC50 values compared to MPM-SeNPs; IC50 of 11.54 ± 1.74 and 31.27 ± 2.9 μg mL−1 compared to 71.4 ± 3.4 μg mL−1, respectively. MPM-SeNPs and PEG-MPM-SeNPs caused apoptosis to MDA-MB-231 cells with a significant decrease in the mitochondrial membrane potential (MMP), increase in the released cytochrome C (Cyt C), and activation of caspase-3/9 (P < 0.05). Linking DOX to PEG-MPM-SeNPs led to an increase in caspase-3/8 concentrations and an increase in the released Cyt C, but there were non-significant differences in MMP (P > 0.1) between treated and untreated control cancer cells. MPM-SeNPs and PEG-MPM-SeNPs caused apoptotic reactions via an intrinsic pathway, while linking DOX to PEG-MPM-SeNPs caused apoptosis in cancer cells through an extrinsic pathway.

Kernel-based testing for single-cell differential analysis

Single-cell technologies offer insights into molecular feature distributions, but comparing them poses challenges. We propose a kernel-testing framework for non-linear cell-wise distribution comparison, analyzing gene expression and epigenomic modifications. Our method allows feature-wise and global transcriptome/epigenome comparisons, revealing cell population heterogeneities. Using a classifier based on embedding variability, we identify transitions in cell states, overcoming limitations of traditional single-cell analysis. Applied to single-cell ChIP-Seq data, our approach identifies untreated breast cancer cells with an epigenomic profile resembling persister cells. This demonstrates the effectiveness of kernel testing in uncovering subtle population variations that might be missed by other methods.

Anticancer Effects of Ethanolic Extracts of Macaranga Peltata Leaves on Human Oral Squamous Carcinoma Cell Lines: An In Vitro Study

ABSTRACT Cancer is a disease resulting from the disruption of cell cycle regulation, leading to the abnormal and unchecked proliferation of cells. Medicinal plants are rich in various bioactive phytochemicals or nutritional compounds. The aim is to determine the cytotoxic and genotoxic effects of ethanolic extracts of Macaranga peltata leaves on human oral cancer cell lines. The study setting was centre for Research on Molecular and Applied Sciences, Azeezia College of Dental Sciences and Research. The study design is a Comparative In Vitro study. Shade dried leaves of Macaranga peltata were subjected to Soxhlet extraction, and ethanolic extract was prepared. In vitro cytotoxic effects on human oral cancer cell lines were evaluated by (3-(4,5-dimethyl thiazole-2yl)-2,5–diphenyl tetrazolium bromide) MTT assay, and genotoxic effect was evaluated by comet assay. Untreated cell lines were used as control, and 5-fluorouracil was used as positive control. All experiments were performed in triplicates, and results were represented as Mean+/- SE. One-way ANOVA and Dunnet test were performed to analyze data. ***P &lt; 0.001 compared with the control group. The ethanolic extract of Macaranga peltata exhibited cytotoxicity against oral cancer cells (LC50: 40.193089 μg/ml). There was a concentration-dependent increase in cell death, and at 100 μg/ml, the extract was most effective, causing 50% inhibition of viability. The comet assay showed significant genotoxic effects compared with 5-fluorouracil and untreated oral cancer cell lines. The ethanolic extract of Macaranga peltata leaves was subjected to MTT assay and comet using KB cell lines. The study concludes that the extract gave promising result for the anticancer activity on the KB cell lines producing cytotoxicity and genotoxicity.

Malignance-restriction activity exhibited by bioactive compounds of selected actinobacteria as silver nanoparticles against A549 lung cancer cell lines.

This article deals with the antibacterial and anticancer potential of secondary metabolites produced by actinomycetes also reported as actinobacteria, Microbacterium proteolyticum (MN560041), and Streptomycetes rochei, where preliminary studies were done with the well diffusion method. These actinobacteria's silver nanoparticles were synthesized and characterized using transmission electron microscopy (TEM) and UV-Visible spectroscopy. Anticancer was measured using the MTT test, reactive oxygen species (ROS) generation measured with DCFDA, mitochondrial membrane potential (MMP) measurement, and DAPI fluorescence intensity activity was measured in treated and non-treated cancerous cells. The IC50 value for 5-FU (a), LA2(O) (b), LA2(R) (c), LA2(ON) (d), and LA2(RN) (e) was obtained at 3.91 μg/mL (52.73% cell viability), 56.12 μg/mL (52.35% cell viability), 44.90 μg/mL (52.3% cell viability), 3.45 μg/mL (50.25% cell viability), and 8.05 μg/mL (48.72% cell viability), respectively. TEM micrographs revealed discrete, well-separated AgNPs particles of size 7.88 ± 2 to 12.86 ± 0.24 nm. Gas chromatography-mass spectrometry was also performed to detect the compounds in bioactive metabolites where n-hexadecanoic acid was obtained as the most significant one. MTT test showed a substantial decline in A549 cell viability (up to 48.72%), 2.75-fold increase in ROS generation was noticed in comparison to untreated A549 lung cancer cells when measured with DCFDA. A total of 0.31-fold decrease in MMP and 1.74-fold increase in DAPI fluorescence intensity compared to untreated A549 lung cancer cells suggests that the synthesized nanoparticles promote apoptosis in cancerous cells. Our findings suggests that the secondary metabolites of M. proteolyticum and S. rochei in nanoparticle form can be used as a significant compound against lung cancers.

Ezetimibe inhibits the migration and invasion of triple-negative breast cancer cells by targeting TGFβ2 andEMT.

The important role of cholesterol in tumor metastasis has been widely studied in recent years. Ezetimibe is currently the only selective cholesterol uptake inhibitor on the market. Here, we explored the effect of ezetimibe on breast cancer metastasis by studying its impact on breast cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT). Differential gene expression analysis and validation were also carried out to compare ezetimibe-treated and untreated breast cancer cells. Finally, breast cancer cells overexpressing TGFβ2 were constructed, and the effect of TGFβ2 on the migration and invasion of ezetimibe-treated breast cancer cells was examined. Our results show that ezetimibe treatment of breast cancer cells inhibited cell migration, invasion, and EMT, and it significantly suppressed the expression of TGFβ2. Overexpression of TGFβ2 reversed the inhibitory effect of ezetimibe on the migration and invasion of breast cancer cells. Taken together, our results suggest that ezetimibe might be a potential candidate for the treatment of breast cancer metastasis.

Gemcitabine-loaded niosomes: Optimization, characterization, and in vitro efficacy against invasive malignancies

Gemcitabine (dFdC) is a widely used prodrug against pancreatic cancer and has been investigated against pancreatic, glioblastoma and breast cancer. However, the nature of gemcitabine hinders its incorporation into nanocarriers at high loading levels. This work focuses for the first time on optimizing gemcitabine-loaded stearic acid-based niosomes for enhanced anti-tumor efficacy. The antitumor effect of the optimized formula (dFdC −9 mM ⊂ Nio) was studied against three undruggable cancer cell lines: pancreatic cancer (PANC-1), glioblastoma (U-87), and triple negative breast cancer (MDA-MB-231), and against normal fibroblasts (HDF). The size of dFdC −9 mM ⊂ Nio formula was 151.3 ± 3.3 nm, the encapsulation efficiency was 68.83 ± 0.08%, and the drug loading capacity was 16.5 ± 0.7%. Cellular uptake of dFdC −9 mM ⊂ Nio by PANC-1 was found to increase 3-fold relative to the untreated cancer cell lines. A positive correlation between cellular uptake and increased cytotoxicity was observed, along with a significant reduction in IC50 values compared to the free form gemcitabine in all three cell lines. Moreover, the overall apoptotic populations in each of the cancer cell lines revealed a statistical difference in PANC-1 (p-value: 0.0451), U-87 (p-value: 0.0497), and MDA-MB-231 (p-value: 0.048) between dFdc and dFdC −9 mM ⊂ Nio treated groups. These results propose stearic acid-based niosomes as a biocompatible drug delivery system for gemcitabine, with a promising potential in enhancing its anti-tumor outcome, especially against pancreatic cancer and glioblastoma.

Abstract 2035: A Benzenesulfornamide with potential to improve chemoresponse of ovarian cancer through activation of AMPK and immunogenic cell death

Abstract Introduction: Ovarian cancer is a leading cause of death among women globally often characterized by poor prognosis and aggressive tumor growth. The therapeutic outcomes of ovarian cancer patients are limited by the development of acquired chemoresistance and the lack of targeted therapies. This study aimed to understand the mechanism in which a benzenesulfornamide named Y3 enhances the efficacy of chemotherapeutic agents. Y3 was previously identified by our team as an activator of AMPK with the activity to induce immunogenic cell death of ovarian cancer cells. Material and Methods: Patient-derived ovarian cancer cell lines were pretreated with Y3 for 3 h before treatment of carboplatin or paclitaxel. Celltiter Glo assay was performed to determine the impact of Y3 pretreatment on the IC50 values of carboplatin or paclitaxel after 48 h. Apoptosis was evaluated using Annexin VI/PI staining and Caspase 3 activity assays. The role of AMPK pathway was assessed using AMPK siRNAs and western blot. The potential of Y3 to enhance immunogenic cell death induced by carboplatin or paclitaxel was evaluated in a syngeneic mouse model of ovarian cancer using a vaccination assay. The control group mice were vaccinated by subcutaneously injecting mouse ovarian cancer cells treated by carboplatin in vitro for 24 h into the left flank. The test group mice were vaccinated by injecting Y3-carboplatin co-treated cells. One week after vaccination, untreated live cancer cells were injected into the right flank of both groups. Tumor growth was monitored. Results: Ovarian cancer cell lines pretreated with Y3 showed decreased IC50 values for carboplatin and paclitaxel treatments. The apoptotic cell populations stained by Annexin VI were increased in the Y3 pretreated in comparisons with the single treatment groups. Caspase-3 activity validated the results of Annexin VI/PI staining assay. AMPK knockdown by siRNAs effectively reduced the levels of phospho-AMPK that was induced by Y3, which also dampened the Y3-promoted chemotherapeutic effects on ovarian cancer cells. In the in vivo vaccination assay, tumor growth in the right flank was suppressed in the mice vaccinated with Y3-carboplatin co-treated cells to an extend that is more significant than the control group. Conclusion: Y3 pretreatment increased the sensitivity of ovarian cancer cell lines to carboplatin and paclitaxel. The effects of Y3 on ovarian cancer cells depend on the activation of AMPK. Y3 enhances the immunogenicity of carboplatin-treated ovarian cancer cells. Citation Format: Juhyun Kim, Nia Montero, Shefali Sharma, Miranda Mansolf, Kevin Yang, Tobias Hartwich, Yang Yang-Hartwich. A Benzenesulfornamide with potential to improve chemoresponse of ovarian cancer through activation of AMPK and immunogenic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2035.

MicroRNA-1 Inhibits the Growth of Breast Cancer Cells MDA-MB-231 and MCF-7 Treated with Hydatid Cyst Fluid.

Antigens in hydatid cyst fluid (HCF) have been discovered to bear a significant resemblance to antigens present in cancer cells. MicroRNA-1 (miR-1) is a well-known member of the tumor inhibitor miRNA family and has been shown to have pro-apoptotic and tumor-inhibitory functions. This study aimed to evaluate the ability of HCF to prevent breast cancer and to explore the underlying mechanisms that affect cancer cells. For this study, MDA-MB-231 and MCF-7 breast cancer cells were cultured and divided into two groups: one group received HCF treatment and the other group was untreated and served as the control group. The cytotoxicity and cell viability of various HCF concentrations on breast cancer cells were evaluated using the MTT assay. In addition, the expression level of miR-1 in HCF-treated and untreated breast cancer cells was analyzed using qRT-PCR. The study found that HCF treatment reduced the growth of MDA-MB-231 and MCF-7 breast cancer cells, indicating that it was cytotoxic to the cells. Specifically, the IC50 concentration of HCF after 24 hours of treatment was 7.32 µg/mL for MDA-MB-231 cells and 13.63 µg/mL for MCF-7 cells. In addition, qRT-PCR analysis revealed that the expression level of miR-1 was significantly increased in HCF-treated MDA-MB-231 (P=0.0203) and MCF-7 (P=0.0394) cell lines compared to untreated controls. Although HCF has been shown to inhibit the growth of breast cancer cells and to upregulate miR-1, a key tumor suppressor in cancer cells, the specific mechanisms responsible for this effect remain unclear. Further studies are needed to fully understand the molecular pathways underlying HCF's antitumor activity and its potential as a therapeutic agent in cancer therapy.

The Influence of Lactobacillus spp. Secondary Metabolites Isolated from Immature Egyptian Honey on Human Pathogens, Transcription of Virulence Genes and Lung Cancer

This work aimed to isolate, and identify Lactic Acid Bacteria LAB from Egyptian immature citrus honey, and characterize their secondary metabolites, as well as determine the antibacterial activities and transcription of virulence genes (stx1, stx2, and eae) influenced by these bacterial secondary metabolites. From twenty hives, twenty immature citrus bee honey samples were taken. Traditional cultural and biochemical testing were used, followed by molecular confirmation. Further, LAB isolates' antibacterial and cytotoxic properties were investigated. 16S rRNA gene sequencing were assessed and, two lactic acid bacterial isolates were identified as Lactobacillus acidophilus Ch2 and Levilactobacillus brevis Ch1. Both isolates have good antagonistic action against clinical pathogens, with Levilactobacillus brevis Ch1 exhibiting the best antibacterial activity against all indicator pathogens examined. When compared to untreated cancer cells, the isolates demonstrated significant cytotoxic activity. Ch1 and Ch2 cell viability percentages were 39.5% and 18.76%, respectively. Furthermore, when exposed to Levilactobacillus brevis Ch1 metabolites, Shiga-producing Escherichia coli (STEC) virulence gene expression was suppressed. To identify bacterial secondary metabolites, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) approach was developed. Twenty-seven metabolites from diverse chemical classes were discovered in the crude extracts with antibacterial and anticancer characteristics. This is the first thorough investigation on the metabolic profile of LAB isolated from immature Egyptian honey and the findings suggested that isolates or their secondary metabolites could be used in the food sector as medicinal alternatives or as a biocontrol agent.

Salvia officinalis L. exerts oncostatic effects in rodent and in vitro models of breast carcinoma.

Introduction: Based on extensive data from oncology research, the use of phytochemicals or plant-based nutraceuticals is considered an innovative tool for cancer management. This research aimed to analyze the oncostatic properties of Salvia officinalis L. [Lamiaceae; Salviae officinalis herba] using animal and in vitro models of breast carcinoma (BC). Methods: The effects of dietary administered S. officinalis in two concentrations (0.1%/SAL 0.1/and 1%/SAL 1/) were assessed in both syngeneic 4T1 mouse and chemically induced rat models of BC. The histopathological and molecular evaluations of rodent carcinoma specimens were performed after the autopsy. Besides, numerous in vitro analyses using two human cancer cell lines were performed. Results and Conclusion: The dominant metabolites found in S. officinalis propylene glycol extract (SPGE) were representatives of phenolics, specifically rosmarinic, protocatechuic, and salicylic acids. Furthermore, the occurrence of triterpenoids ursolic and oleanolic acid was proved in SPGE. In a mouse model, a non-significant tumor volume decrease after S. officinalis treatment was associated with a significant reduction in the mitotic activity index of 4T1 tumors by 37.5% (SAL 0.1) and 31.5% (SAL 1) vs. controls (set as a blank group with not applied salvia in the diet). In addition, salvia at higher doses significantly decreased necrosis/whole tumor area ratio by 46% when compared to control tumor samples. In a rat chemoprevention study, S. officinalis at a higher dose significantly lengthened the latency of tumors by 8.5 days and significantly improved the high/low-grade carcinomas ratio vs. controls in both doses. Analyses of the mechanisms of anticancer activities of S. officinalis included well-validated prognostic, predictive, and diagnostic biomarkers that are applied in both oncology practice and preclinical investigation. Our assessment in vivo revealed numerous significant changes after a comparison of treated vs. untreated cancer cells. In this regard, we found an overexpression in caspase-3, an increased Bax/Bcl-2 ratio, and a decrease in MDA, ALDH1, and EpCam expression. In addition, salvia reduced TGF-β serum levels in rats (decrease in IL-6 and TNF-α levels were with borderline significance). Evaluation of epigenetic modifications in rat cancer specimens in vivo revealed a decline in the lysine methylations of H3K4m3 and an increase in lysine acetylation in H4K16ac levels in treated groups. Salvia decreased the relative levels of oncogenic miR21 and tumor-suppressive miR145 (miR210, miR22, miR34a, and miR155 were not significantly altered). The methylation of ATM and PTEN promoters was decreased after S. officinalis treatment (PITX2, RASSF1, and TIMP3 promoters were not altered). Analyzing plasma metabolomics profile in tumor-bearing rats, we found reduced levels of ketoacids derived from BCAAs after salvia treatment. In vitro analyses revealed significant anti-cancer effects of SPGE extract in MCF-7 and MDA-MB-231 cell lines (cytotoxicity, caspase-3/-7, Bcl-2, Annexin V/PI, cell cycle, BrdU, and mitochondrial membrane potential). Our study demonstrates the significant chemopreventive and treatment effects of salvia haulm using animal or in vitro BC models.

The inhibition effects of Lentilactobacillus buchneri-derived membrane vesicles on AGS and HT-29 cancer cells by inducing cell apoptosis

In recent years, probiotics and their derivatives have been recognized as important therapeutic agents in the fight against cancer. Therefore, this study aimed to investigate the anticancer effects of membrane vesicles (MVs) from Lentilactobacillus buchneri strain HBUM07105 probiotic isolated from conventional and unprocessed yogurt in Arak province, Iran, against gastric and colon cancer cell lines. The MVs were prepared from the cell-free supernatant (CFS) of L. buchneri and characterized using field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) and SPS-PAGE techniques. The anticancer activity of MVs was evaluated using MTT, flow cytometry, qRT-PCR techniques, and a scratch assay. The study investigated the anti-adenocarcinoma effect of MVs isolated from L. buchneri on a human gastric adenocarcinoma cell line (AGS) and a human colorectal adenocarcinoma cell line (HT-29) at 24, 48, and 72-h time intervals. The results demonstrated that all prepared concentrations (12.5, 25, 50, 100, and 200 µg/mL) of MVs reduced the viability of both types of human adenocarcinoma cells after 24, 48, and 72 h of treatment. The analysis of the apoptosis results revealed that the percentage of AGS and HT-29 cancer cells in the early and late stages of apoptosis was significantly higher after 24, 48, and 72 h of treatment compared to the untreated cancer cells. After treating both AGS and HT-29 cells with the MVs, the cells were arrested in the G0/G1 phase. These microvesicles demonstrate apoptotic activity by increasing the expression of pro-apoptotic genes (BAX, CASP3, and CASP9). According to the scratch test, MVs can significantly decrease the migration of HT-29 and AGS cancer cells after 24, 48, and 72 h of incubation compared to the control groups. The MVs of L. buchneri can also be considered a potential option for inhibiting cancer cell activities.

Modifications of DAMPs levels in extracellular environment induced by aminolevulinic acid-based photodynamic therapy of esophageal cancer cells

Purpose Immunogenic cell death plays an important role in anticancer treatment because it combines cell death with appearance of damage associated molecular patterns that have the potential to activate anticancer immunity. Effects of damage associated molecular patterns induced by aminolevulinic acid-based photodynamic therapy were studied mainly on dendritic cells. They have not been deeply studied on macrophages that constitute the essential component of the tumor microenvironment. The aim of this study was to analyze features of esophageal cancer cell death in relation to release capacity of damage associated molecular pattern species, and to test the effect of related extracellular environmental alterations on macrophages. Material and methods Esophageal Kyse 450 carcinoma cells were subjected to aminolevulinic acid-based photodynamic therapy at different concentrations of aminolevulinic acid. Resting, IFN/LPS and IL-4 macrophage subtypes were prepared from monocytic THP-1 cell line. Cell death features and macrophage modifications were analyzed by fluorescence-based live cell imaging. ATP and HMGB1 levels in cell culture media were determined by ELISA assays. The presence of lipid peroxidation products in culture media was assessed by spectrophotometric detection of thiobarbituric acid reactive substances. Results Aminolevulinic acid-based photodynamic therapy induced various death pathways in Kyse 450 cells that included features of apoptosis, necrosis and ferroptosis. ATP amounts in extracellular environment of treated Kyse 450 cells increased with increasing aminolevulinic acid concentration. Levels of HMGB1, detectable by ELISA assay in culture media, were decreased after the treatment. Aminolevulinic acid-based photodynamic therapy induced lipid peroxidation of cellular structures and increased levels of extracellular lipid peroxidation products. Incubation of resting and IL-4 macrophages in conditioned medium from Kyse 450 cells treated by aminolevulinic acid-based photodynamic therapy induced morphological changes in macrophages, however, comparable alterations were induced also by conditioned medium from untreated cancer cells. Conclusion Aminolevulinic acid-based photodynamic therapy leads to alterations in local extracellular levels of damage associated molecular patterns, however, comprehensive studies are needed to find whether they can be responsible for macrophage phenotype modifications.

Unlocking the therapeutic potential of drug combinations through synergy prediction using graph transformer networks

Drug combinations are frequently used to treat cancer to reduce side effects and increase efficacy. The experimental discovery of drug combination synergy is time-consuming and expensive for large datasets. Therefore, an efficient and reliable computational approach is required to investigate these drug combinations. Advancements in deep learning can handle large datasets with various biological problems. In this study, we developed a SynergyGTN model based on the Graph Transformer Network to predict the synergistic drug combinations against an untreated cancer cell line expression profile. We represent the drug via a graph, with each node and edge of the graph containing nine types of atomic feature vectors and four bonds features, respectively. The cell lines represent based on their gene expression profiles. The drug graph was passed through the GTN layers to extract a generalized feature map for each drug pairs. The drug pair extracted features and cell-line gene expression profiles were concatenated and subsequently subjected to processing through multiple densely connected layers. SynergyGTN outperformed the state-of-the-art methods, with a receiver operating characteristic area under the curve improvement of 5% on the 5-fold cross-validation. The accuracy of SynergyGTN was further verified through three types of cross-validation tests strategies namely leave-drug-out, leave-combination-out, and leave-tissue-out, resulting in improvement in accuracy of 8%, 1%, and 2%, respectively. The Astrazeneca Dream dataset was utilized as an independent dataset to validate and assess the generalizability of the proposed method, resulting in an improvement in balanced accuracy of 13%. In conclusion, SynergyGTN is a reliable and efficient computational approach for predicting drug combination synergy in cancer treatment. Finally, we developed a web server tool to facilitate the pharmaceutical industry and researchers, as available at: http://nsclbio.jbnu.ac.kr/tools/SynergyGTN/.

Extracellular vesicles derived from oxidatively stressed stromal cells promote cancer progression

Like many diseases, cancer is influenced by oxidative stress. Increases in oxidative stress caused by factors such as environmental stressors and unhealthy diets can increase the risk of cancer and worsen cancer prognoses. However, oxidative stress does not always promote cancer. On the contrary, many chemotherapeutics induce the production of oxidative stress to kill cancer cells. The tumor microenvironment (TME) is another factor in cancer progression. Stromal cells, a part of the TME, communicate with cancer cells through extracellular vesicles (EVs) - the primary vehicles for the delivery of messengers, including proteins, metabolites, DNA, and RNA. We hypothesized that the TME mediates cancer’s response to oxidative stress by delivering EVs to cancer cells. In order to test this hypothesis, we treated breast cancer cells (HCC1806, SKBR3, MCF7, and MDA-MB-436) and lung cancer cells (A549 and PC9) with EVs derived from oxidatively stressed stromal cells and compared their expression of marker proteins of cell proliferation and epithelial to mesenchymal transition to cancer cells treated with EVs from control stromal cells and untreated cancer cells. We found that EVs extracted from oxidatively stressed adipocytes increased the cell proliferation of breast cancer cells. Additionally, we found that EVs extracted from lung fibroblasts promoted epithelialmesenchymal transition in lung cancer cells. These findings present a novel way that the TME influences cancer progression. The findings of this paper can inform future cancer prevention studies.

ANALYZING STAT-3 GENE EXPRESSION IN ORAL SQUAMOUS CELL CARCINOMA CELLS PRE- AND POST-CARBOPLATIN TREATMENT IN VITRO

Aim: Oral squamous cell carcinoma (OSCC) represents a small percentage of global cancer cases, with oral tumors being the most common. OSCC can be caused by various factors including tobacco, alcohol, and viral infections. Carboplatin, a platinum-based chemotherapy drug, shows promise in treating OSCC with fewer side effects. However, activation of Signal Transducer and Activator of Transcription 3 (STAT3) in OSCC cells can hinder carboplatin's effectiveness. This study aims to assess carboplatin's efficacy in OSCC treatment and explore the potential benefits of combining it with STAT3 inhibitors. Materials and methods: KB cells were subjected to treatment with varying concentrations of carboplatin. Cell proliferation was evaluated through the MTT assay, while RNA isolation was performed using the TRIzol method followed by cDNA conversion. Gene expression analysis was carried out using qRT-PCR. Statistical analysis of the results was conducted using SPSS. Results: The significant reduction in STAT3 expression post-treatment compared to untreated cancer cells indicates a promising avenue for further exploration of carboplatin’s therapeutic efficacy in targeting oncogenic signaling pathways. Conclusion: The results show a significant decrease in STAT3 expression post-treatment compared to untreated OSCC cells, suggesting carboplatin's strong anti-cancer effect and its potential as a therapeutic option for OSCC treatment.

The dual activity of CaONPs as a cancer treatment substance and at the same time resistance to harmful microbes

Nanotechnology holds significant promise for the development of novel and necessary products that enhance human health. Pharmacology and nanotechnology have contributed to developing advanced and highly effective drugs for cancer treatment and combating microbial infections. The microbiological effectiveness against the variety of examined microorganisms was assessed using the time killer curve, scanning electron microscopy (SEM), MIC techniques, and the agar well diffusion method. SEM was utilized to enhance the analysis of the mechanisms underlying the bio-interface interaction and intracellular localization of calcium oxide nanoparticles (CaONPs). The MTT test was used to examine the cytotoxicity of CaONP anticancer activity in various cancer cells, including colon, breast, and hepatic cells. The efficacy of CaONPs as an anticancer medication was elucidated by analyzing the gene expression of both treated and untreated cancer cells. MIC and MBC of CaONPs against Escherichia coli and Staphylococcus epidermidis were 150, 150, 150, and 200 µg/ml, respectively. The MIC and MFC of CaONPs against Candida albicans were 200 µg/ml and 250 µg/ml, respectively. The IC50 values of various CaONPs vary depending on the type of cancer cells. The gene expression analysis of breast cancer cells undergoing treatment revealed the identification of several cancer-controlling genes, namely BAX, BCL2, P53, TERT, KRAS1, KRAS2, and RB1. The study demonstrated the notable antibacterial efficacy of CaONPs, highlighting their potential as cancer therapies.

Dual Role of Vitamin C-Encapsulated Liposomal Berberine in Effective Colon Anticancer Immunotherapy.

The aim of the study was to achieve effective colon anticancer immunotherapy using the alkaloid berberine. In the presented paper we attempt to develop a formulation of berberine loaded into liposomal carriers using the vitamin C gradient method, characterized by efficient drug encapsulation, high stability during long-term storage, low drug release in human plasma with specific cytotoxicity towards colon cancer cells. Liposomal berberine was responsible for the induction of oxidative stress, the presence of Ca2+ ions in the cytosol, the reduction of Δψm, and ATP depletion with a simultaneous lack of caspase activity. Moreover, treatment with liposomal berberine led to CRT exposure on the surface of cancer cells, extracellular ATP, and HMGB1 release. The above-described mechanism of action was most likely associated with ICD induction, contributing to the increased number of phagocytic cancer cells. We have shown that cancer cells treated with liposomal berberine were phagocytosed more frequently by macrophages compared to the untreated cancer cells. What is more, we have shown that macrophage pre-treatment with liposomal berberine led to a 3-fold change in the number of phagocytosed SW620 cancer cells. The obtained results provide new insights into the role of berberine in maintaining the immune response against colorectal cancer.

Comparison of anti-cancer effects of platinum ribavirin and ribavirin via telomerase and Bcl-2 gene expression.

Among the common treatments for cancers, chemotherapy is widely used. One of the ways to evaluate the effectiveness of anti-cancer drugs is by checking the expression of tumor markers. Hence, this study aimed to evaluate the anti-cancer effects of the newly synthesized platinum ribavirin (Pt-Rb) compared to ribavirin (Rb) through biomarkers. In this study, cell lines were divided into four groups: groups A and B as healthy negative control group and untreated cancer group respectively. Group C and D were treated with, Rb and Pt-Rb, a novel anti-cancer drug, respectively. After evaluating LC50 for the drugs by MTT test, the expression of telomerase and Bcl-2 (B cell lymphoma-2) genes was evaluated using real-time PCR (RT-qPCR). The results showed a significant decrease in telomerase (0.020 ± 0.007) and Bcl-2(0.120 ± 0.005) gene expression in cancer cells treated with Pt-Rb (group D) compared to telomerase (0.040 ± 0.014) and Bcl-2(0.220 ± 0.014) treated with Rb (group C) and also between group D and telomerase (70.76 ± 0.330) and Bcl-2 (99.52 ± 0.670) in group B. The majority of the groups under investigation showed a significant difference (p < 0.05), suggesting that Pt-Rb had stronger anti-cancer effects than Rb and untreated cancer cells. Additionally, Pt-Rb treatment results demonstrated more increased apoptosis than Rb. Our results demonstrated that Pt-Rb is an effective medication in cancer treatment by lowering anti-apoptotic indicators. Therefore, this chemical has the potential to be an effective anti-cancer therapy, pending further research on animal models and then human volunteers.