MCF-7 Cells Research Articles

Benzylpiperazinyl derivatives of alepterolic acid: Synthesis and cytotoxic evaluation.

Natural products play a significant role in the development of modern drugs. Alepterolic acid, a labdane-type diterpenoid firstly isolated from Aleuritopteris argentea (Gmél.) Fée, has been identified as a valuable template for the synthesis of potent anticancer agents by structural modification. In this study, a series of new derivatives was obtained by coupling alepterolic acid with benzylpiperazines. It was found that (3,4-dichlorobenzyl)piperazinyl alepterolic acid (compound 6p) displayed the most toxic against MCF-7 cell line, with IC50 value of 8.31±0.67 μM. Further investigations demonstrated that compound 6p induced morphological changes in MCF-7 cells, inhibited proliferation in a time- and dose-dependent manner. Furthermore, western blot analysis revealed that compound 6p induced a significant increase in cleaved caspase-9, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) and Bax/Bcl2 ratio in MCF-7 cells. All of these results confirmed that compound 6p induced endogenous apoptosis in MCF-7 cells. Conclusively, the findings suggest that the incorporation of benzylpiperazine to alepterolic acid represents a promising approach for the discovery of new drug candidates.

Activation of estrogen-related receptor γ by calcium and cadmium.

Estrogen-related receptor γ (ERRγ) is a metabolic regulator with no identified physiological ligands. This study investigates whether calcium is an ERRγ ligand that mediates the effects of glucagon and whether cadmium, which mimics the effects of calcium, disrupts metabolism through ERRγ. HepG2, MCF-7, and HEK293T transfected with ERRγ were treated with glucagon, calcium, cadmium, ERRγ agonist, or ERRγ inhibitor. Cells were then collected for in vitro assays including real-time qPCR, Western blot, ChIP, immunofluorescence, mutational analysis, or gene set enrichment analysis. Molecular dynamics simulations were performed to study mutation sites. In HepG2 cells, treatment with glucagon, calcium, or cadmium re-localized ERRγ to the cell nucleus, recruited ERRγ to estrogen-related response elements, induced the expression of ERRγ-regulated genes, and increased extracellular glucose that was blocked by an ERRγ antagonist. In MCF-7 cells and HEK293T cells transfected with ERRγ, similar treatments induced the expression of metabolic genes. Mutational analysis identified S303, T429, and E452 in the ligand-binding domain as potential interaction sites. Molecular dynamics simulations showed that calcium induced changes in ERRγ similar to ERRγ agonist. The results suggest that calcium is a potential ligand of ERRγ that mediates the effects of glucagon and cadmium disrupts metabolism through ERRγ.

Integrated RNA Sequencing Analysis Revealed Early Gene Expression Shifts Associated with Cancer Progression in MCF-7 Breast Cancer Cells Cocultured with Adipose-Derived Stem Cells

Breast cancer remains a prevalent global health challenge, with tumor-removal surgeries being among the most common treatments but often leading to aesthetic defects. Adipose-derived stem cell (ADSC)-enriched fat grafting in breast reconstruction offers promising therapeutic benefits. However, concerns about its oncological safety persist, particularly regarding the potential risks of promoting cancer recurrence. This study investigated the effects of ADSCs on breast cancer progression by coculturing ADSCs with the MCF-7 breast cancer cell line for a short cell cultivation period of 3 days. We performed an RNA-seq analysis to identify significant transcriptomic changes in cocultured MCF-7 cells and carried out functional enrichment analyses to uncover key biological pathways influenced by ADSCs. Our findings revealed that transcriptomic alterations in MCF-7 cells are linked to aggressive cancer traits, including the upregulation of epithelial–mesenchymal transition (EMT) and the HIF-1 signaling pathway, which indicate a shift toward aerobic glycolysis. Some of the observed gene expression changes also correlated with relapse risk and mortality. These findings underscore the need for further research to explore the implications of these genes and pathways in driving aggressive cancer phenotypes and assess the safety of ADSCs in clinical settings.

Hypoxia-Active Iridium(III) Bis-terpyridine Complexes Bearing Oligothienyl Substituents: Synthesis, Photophysics, and Phototoxicity toward Cancer Cells.

In an effort to develop hypoxia-active iridium(III) complexes with long visible-light absorption, we synthesized and characterized five bis(terpyridine) Ir(III) complexes bearing oligothienyl substituents on one of the terpyridine ligands, i.e., nT-Ir (n = 0-4). The UV-vis absorption, emission, and transient absorption spectroscopy were employed to characterize the singlet and triplet excited states of these complexes and to explore the effects of varied number of thienyl units on the photophysical parameters of the complexes. In vitro photodynamic therapeutic activities of these complexes were assessed with respect to three melanoma cell lines (SKMEL28, A375, and B16F10) and two breast cancer cell lines (MDA-MB-231 and MCF-7) under normoxia (∼18.5% oxygen tension) and hypoxia (1% oxygen tension) upon broadband visible (400-700 nm), blue (453 nm), green (523 nm), and red (633 nm) light activation. It was revealed that the increased number of thienyl units bathochromically shifted the low-energy absorption bands to the green/orange spectral regions and the emission bands to the near-infrared (NIR) regions. The lowest triplet excited-state lifetimes and the singlet oxygen generation efficiency also increased from 0T to 2T substitution but decreased in 3T and 4T substitution. All complexes exhibited low dark cytotoxicity toward all cell lines, but 2T-Ir-4T-Ir manifested high photocytotoxicity for all cell lines upon visible, blue, and green light activation under normoxia, with 2T-Ir showing the strongest photocytotoxicity toward SKMEL28, MDA-MB-231, and MCF-7 cells, and 4T-Ir being the most photocytotoxic one for B16F10 and A375 cells. Singlet oxygen, superoxide anion radicals, and peroxynitrite anions were found to likely be involved in the photocytotoxicity exhibited by the complexes. 4T-Ir also showed strong photocytotoxicity upon red-light excitation toward all cell lines under normoxia and retained its photocytotoxicity under hypoxia toward all cell lines upon visible, blue, and green light excitation. The hypoxic activity of 4T-Ir along with its green to orange light absorption, NIR emission, and low dark cytotoxicity suggest its potential as a photosensitizer for photodynamic therapy applications.

Dual Recognition Strategy-Based Ratiometric Electrochemical Assay for Ultrasensitive and Accurate Detection of Specific Circulating Tumor Cells.

Sensitive, specific, and accurate detection of circulating tumor cells (CTCs) is of great importance in the diagnosis and prognosis of cancer. Herein, an ultrasensitive ratiometric electrochemical biosensor was designed with a dual recognition strategy for highly specific and accurate detection of circulating MCF-7 human breast cancer cells based on gold film-modified porous organic cages loaded with ferrocene (Au/Fc@POCs) as the substrate and methylene blue-encapsulated covalent organic frameworks (MB@COFs) as the label material, producing two independent electrochemical signals from the Fc and MB probes, respectively. As the concentration of MCF-7 cells increases, the electrochemical signal of MB enhances significantly while the oxidation signal of Fc decreases remarkably. Under optimal experimental conditions, the ratios (IMB/IFc) between the double signals showed a broad dynamic range of 10 to 1 × 107 cells/mL with an effectively lower detection limit of 1 cells/mL (S/N = 3). Furthermore, the biosensor was able to accurately enumerate MCF-7 cells in human serum samples with excellent results. In this work, the developed ratiometric electrochemical biosensor offers a reliable and sensitive strategy for the quantitative determination of circulating MCF-7 human breast cancer cells as well as an effective approach for the clinical detection of rare cancer cells, especially in early stage cancer diagnosis.

Chemical Composition, Anti-microbial, and Cytotoxic Activities of Essential Oil from Magnolia bidoupensis Q. N. Vu leaves, an Endemic Species to the Central Highlands of Vietnam.

An analysis was conducted on the essential oil extracted from the leaves of Magnolia bidoupensis utilizing GC-MS, revealing thirty-three constituents that account for 98.9% of the essential oil. The main components included pogostol (22.4%), δ-selinene (16.2%), and α-amorphene (14.7%). Bioassays were then performed to evaluate the oil's biological activity. The essential oil exhibited antimicrobial activity against all tested microorganisms (six bacterial strains and one fungal strain) using the minimum inhibitory concentration (MIC) method. Additional cytotoxicity tests were conducted on KB, HepG2, MCF-7, and A549 cancer cell lines using the MTT method. The essential oil exhibited strong cytotoxic effects on all four cell lines, with IC50 values ranging from 1.37 ± 0.05 μg/mL (KB) to 2.40 ± 0.06 μg/mL (A549).

Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo.

Cucurbitacin B (CuB) is a natural triterpenoid with diverse pharmacological effects including potent anticancer activity. However, its oral bioavailability is hampered by limited metabolism in vivo. We characterized CuB's in vivo metabolism in rats to uncover bioactive metabolites retaining therapeutic potential, using a robust UHPLC-Q-TOF-MS/MS workflow. This workflow combined molecular networking, fragmentation filtering, and mass defect filtering to identify CuB metabolites in rat urine, plasma, and feces following oral administration. Thirteen metabolites were identified and seven were confirmed. Major phase I transformations involved hydrolysis, reduction, epoxidation, and amination. Phase II conjugation included cysteine, glutathione, glucuronide, and gluconic acid conjugates. Notably, one of the main metabolites formed was the cysteine conjugate CuB-Cys. CuB-Cys maintained similar in vitro antiproliferative activity to CuB on HepG2, MCF-7, and PANC-1 cancer cell lines. However, it demonstrated lower cytotoxicity towards non-cancerous L02 cells, highlighting improved therapeutic selectivity. Mechanistically, CuB-Cys induced greater apoptotic signaling in HepG2 cells than CuB via enhanced caspase activation and disrupted BAX-Bcl-2 balance. This represents the first systematic characterization of CuB's in vivo metabolic pathway. The identification and confirmation of CuB-Cys provide insight for drug development efforts aiming to maintain therapeutic efficacy while reducing toxicity, via metabolite-based approaches. Our findings shed light on strategies for improving CuB's clinical potential.

Comprehensive study of the physicochemical properties of three-component deep eutectic solvents and their implications for microbial and anticancerous activity

Sustainable chemistry centers on substituting perilous solvents and materials with eco-conscious alternatives. Deep eutectic solvents (DES) hold substantial potential in this arena. This inquiry includes the formulation of three-component eutectic solvents and an exhaustive scrutiny of their physical and chemical attributes. These encompass solubility, boiling point, pH, density, viscosity, surface tension, refractive index, contact angle, conductivity, Fourier-transform infrared spectroscopy, polarized optical microscopy, thermogravimetric analysis, and differential scanning calorimetry. Furthermore, a biological exploration featured two bacterial strains and two fungal strains. The entire spectrum of ten three-component DES was administered to these microorganisms to discern plausible impacts. In addition, the biomedical promise of these DES was unveiled through anticancer assays employing MCF-7 and HeLa cell lines. The outcomes were favorable, underscoring robust anticancer potency, thereby hinting at future oncological utility. These interdisciplinary endeavors envelop the progression of sustainable solvent innovation, meticulous physicochemical scrutiny, microbial analysis, and anticancer appraisal. This study propels inventive resolutions with ecological and biomedical reverberations by amalgamating these distinct yet interconnected facets.

Advantages of single high-dose radiation therapy compared with conventional fractionated radiation therapy in overcoming radioresistance

Background Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms. Methods Radioresistant cell lines were previously established by exposing SK-BR-3 and MCF-7 cells to 48 Gy and 70 Gy of radiation, respectively, in multiple fractions. We compared the effects of 2 Gy × 5 and 7 Gy × 1 fractions on these cells using clonogenic survival assays and western blot analysis. In vivo antitumor effects were assessed in SR tumor-bearing BALB/c mice irradiated with either 2 Gy × 5 or 7 Gy × 1 fractions. Results 7 Gy x1 was more efficient at killing radioresistant breast cancer cells than 2 Gy x5. Furthermore, the 7 Gy x1 fraction produced higher levels of reactive oxygen species (ROS) and decreased the expression of radioresistance factors such as p-STAT3, ACSL4, FOXM1, RAD51, Bcl-xL, and survivin. Consistent with the in vitro studies, the 7 Gy × 1 fraction also showed superior antitumor effects in SR tumor-bearing BALB/c mice. Conclusions Single high-dose RT offers superior advantages over conventional fractionated RT in regard to overcoming radioresistance, supporting its potential as a promising treatment for recurrent tumors.

A prospective diagnostic model for breast cancer utilizing machine learning to examine the molecular immune infiltrate in HSPB6

BackgroundBreast cancer is a significant public health issue worldwide, being the most prevalent cancer among women and a leading cause of death related to this disease. The molecular processes that propel breast cancer progression are not fully elucidated, highlighting the intricate nature of the underlying biology and its crucial impact on global health. The objective of this research was to perform bioinformatics analyses on breast cancer-related datasets to gain a comprehensive understanding of the molecular mechanisms at play and to identify key genes associated with the disease.MethodsThe toolkit analyses involve techniques such as differential gene expression analysis, Gene Set Enrichment Analysis (GSEA), Weighted Co-Expression Network Analysis (WGCNA), and Machine Learning algorithms. Furthermore, in vitro cell experiments have demonstrated the impact of HSPB6 on cell migration, proliferation, and apoptosis.ResultsThe study identified multiple genes that displayed differential expression in breast cancer, notably FHL1 and HSPB6. A machine learning model was developed in this study and specifically trained for breast cancer diagnosis using these genes, achieving high precision. Furthermore, analysis of immune cell infiltration revealed an enrichment of Tregs and M2 macrophages in the treated group, showcasing its significant impact on the tumor’s immunological context. A temporal analysis of breast cancer cells using single-cell RNA sequencing provided insights into cellular developmental trajectories and highlighted changes in expression patterns across key genes during disease progression. The upregulation of HSPB6 in MCF7 cells significantly inhibited both cell migration and proliferation abilities, suggesting that promoting HSPB6 expression could induce ferroptosis in breast cancer cells.ConclusionOur findings have identified compelling molecular targets and distinctive diagnostic markers for the clinical management of breast cancer. This data will serve as crucial guidance for further research in the field.

Splicing Dysregulation of Non-Canonical GC-5' Splice Sites of Breast Cancer Susceptibility Genes ATM and PALB2.

Background/Objectives: The non-canonical GC-5' splice sites (5'ss) are the most common exception (~1%) to the classical GT/AG splicing rule. They constitute weak 5'ss and can be regulated by splicing factors, so they are especially sensitive to genetic variations inducing the misrecognition of their respective exons. We aimed to investigate the GC-5'ss of the breast/ovarian cancer susceptibility genes, ATM (exon 50), BRIP1 (exon 1), and PALB2 (exon 12), and their dysregulation induced by DNA variants. Methods: Splicing assays of the minigenes, mgATM_49-52, mgBRIP1_1-2, and mgPALB2_5-12, were conducted to study the regulation of the indicated GC-5'ss. Results: A functional map of the splicing regulatory elements (SRE) formed by overlapping exonic microdeletions revealed three essential intervals, ATM c.7335_7344del, PALB2 c.3229_3258del, and c.3293_3322del, which are likely targets for spliceogenic SRE-variants. We then selected 14 ATM and 9 PALB2 variants (Hexplorer score < -40) located at these intervals that were assayed in MCF-7 cells. Nine ATM and three PALB2 variants affected splicing, impairing the recognition of exons 50 and 12, respectively. Therefore, these variants likely disrupt the active SREs involved in the inclusion of both exons in the mature mRNA. DeepCLIP predictions suggested the participation of several splicing factors in exon recognition, including SRSF1, SRSF2, and SRSF7, involved in the recognition of other GC sites. The ATM spliceogenic variants c.7336G>T (p.(Glu2446Ter)) and c.7340T>A (p.(Leu2447Ter)) produced significant amounts of full-length transcripts (55-59%), which include premature termination stop codons, so they would inactivate ATM through both splicing disruption and protein truncation mechanisms. Conclusions: ATM exon 50 and PALB2 exon 12 require specific sequences for efficient recognition by the splicing machinery. The mapping of SRE-rich intervals in minigenes is a valuable approach for the identification of spliceogenic variants that outperforms any prediction software. Indeed, 12 spliceogenic SRE-variants were identified in the critical intervals.

Dibenzoxanthene-β-lactam hybrids as potential antioxidant and anticancer agents: Synthesis, biological evaluation, and docking study

In this study, we designed and synthesized a series of β-lactam compounds bearing 14-phenyl-14H-dibenzo[a,j]xanthene moiety attached to the N-1 position of the β-lactam ring through a [2 + 2] cycloaddition process. All the synthesized compounds have been characterized by elemental analysis, Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectral analysis. These derivatives were evaluated for their anticancer and antioxidant activities. The in vitro anticancer activity of new compounds was examined against MCF-7 (breast cancer), HepG2 (liver hepatocellular carcinoma), and TC-1 (mouse lung epithelial) cell lines by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Notably, compounds 4c, 4e and 4 g demonstrated significant anticancer activity against TC-1 cell line. Additionally, compounds 4c, 4f and 4 g exhibited promising levels of efficacy against the MCF-7 cell line. The diphenylpicrylhydrazyl (DPPH) radical scavenging assay indicated that 4h and 4i are more potent antioxidant agents than the Vitamin C, while 4a, 4b, 4c, and 4j exhibited moderate antioxidant capabilities. Furthermore, the docking simulations are consistent with the biological assay results, indicating that the hybrids may bind to protein targets through hydrogen bonding and other nonvalent interactions.

New sesquiterpenes from the soft coral Litophyton arboreum.

Two new sesquiterpenes; 8α,11-dihydroxy-β-cyperon (2), and 5-epi-7α-hydroxy-( +)-oplopanone (3), were isolated from the soft coral Litophyton arboreum, together with nine known ones, including five sesquiterpenes; 11-hydroxy-8-oxo-β-cyperon (1), alismoxide (4), 5β,8β-epidioxy-11-hydroxy-6-eudesmene (5), chabrolidione B (6), 7-oxo-tri-nor-eudesm-5-en-4β-ol (7), two sterols; 7β-acetoxy-24-methyl-cholesta-5,24(28)-diene-3β,19-diol (8), nebrosteroid M (9), and two glycerol derivatives; chimyl alcohol (10) and batyl alcohol (11). The structures of the isolated compounds were characterized using spectroscopic techniques, predominately HR-ESI-MS, 1D, 2D-NMR, and ECD analyses. Compounds 1-11 were evaluated for their cytotoxic activity against three human cancer-cell lines (A549, MCF-7 and HepG2), and anti-leishmanial potential against the causal parasite, Leishmania major. Compounds 4, 8, and 9 exhibited potent cytotoxic activity against the A549 cell line (IC50 = 17.0 ± 2.5, 13.5 ± 2.1, and 16.5 ± 1.3μg/ml, respectively) as compared with the standard antitumor agent etoposide (IC50 28.4 ± 4.5μg/ml). In addition, compound 9 exhibited remarkable cytotoxic activity against MCF-7 cell line (IC50 = 24.7 ± 2.1μg/ml: 22.2 ± 4.2μg/mL for etoposide).

Evaluating the Antioxidant Capacity, Phenolic Contents, and Anticancer Potential of Caralluma europaea Extracts

Background: Caralluma europaea (C. europaea) is a genus of shrubs in the Apocynaceae family, endemic to the Mediterranean region. Assessing the anticancer properties, total phenolic and flavonoid content, and antioxidant activity of different C. europaea extracts were the aim of this study.Methods: To determine antioxidant activity, we used three free radical scavenging assays: DPPH (2,2-Diphenyl-1-picrylhydrazyl), hydrogen peroxide (H2O2), and nitric oxide (NO) assays. Total phenolic and flavonoid contents were measured using colorimetric methods. The anti-important activity was evaluated by MTT assay.Results: Our findings showed that the efficacy of the extract in MCF7 cells decreased in the system containing chloroform, methanol, ethyl acetate, and water. The strength of the extract for U87 cells decreased according to methanolic, chloroform and water, where ethyl acetate was the strongest. The highest total phenolic and flavonoid content was found in methanol extract. All extracts showed a high scavenging activity of DPPH. Methanol extract showed the highest antioxidant activity in the NO assay of the solution, followed by ethyl acetate, chloroform, and aqueous extract. In the H2O2-based antioxidant activity assay, the methanol extract again showed the highest activity, followed by ethyl acetate, chloroform, and aqueous extracts.Conclusions: Extracts of C. europaea have shown great potential as natural antioxidants and anticancer agents in this study, suggesting that they deserve further investigation into the food and pharmaceutical fields.Keywords: Phenolic content; Flavonoid content; Antioxidant activity; Anti-cancer activity

Two New Inner-sphere Pt(II) Thiosemicarbazone Schiff Base Complexes Immobilized into Magnetic Nanoparticles: Synthesis, Characterization, and Biological Investigations

This study explores the synthesis, characterization, and biological investigations of two new Pt(II) thiosemicarbazone complexes immobilized in magnetic nanoparticles (MNPs). MNPs exhibit distinctive physical and chemical properties that enhance their interactions with biological targets. These traits make them particularly useful, especially when combined with drugs, increasing therapeutic effectiveness while also serving as efficient diagnostic tools in imaging techniques. The two Pt(II) complexes are represented by the formulas [Pt(HL1)(H2O)]Cl and [Pt(HL2)(H2O)2]Cl. The ligand, H2L1 signifies (Z)-2-(2-oxoindolin-3-ylidene)-N-phenylhydrazine-1-carbothioamide, while H2L2 stands for (Z)-N-ethyl-2-(2-oxoindolin-3-ylidene)hydrazine-1-carbothioamide. The ligands and their Pt(II) complexes were characterized through various techniques, including elemental analysis, mass spectrometry, thermal analysis, powder X-ray diffraction (XRD), FT-IR, NMR, and UV–visible spectroscopy. The two complexes form a square planar geometry, in which H2L1 performs as a mononegative tridentate while H2L2 acts as a mononegative bidentate. Density Functional Theory (DFT) calculations were utilized to investigate the molecular configurations of the ligands and its Pt(II) complexes. The UV–visible and fluorescence spectroscopy techniques were employed to examine the interactions between Pt(II) complexes and Bovine Serum Albumin (BSA). DNA fragmentation studies on the Pt(II) complexes were performed and showed that [Pt(HL2)(H2O)2].Cl complex is the strongest degraded on the DNA. [Pt(HL1)(H2O)]Cl and [Pt(HL2)(H2O)2]Cl complexes were immobilized into MNPs to produce Pt(L1)/MNPs and Pt(L2)/MNPs, respectively. Pt(L1)/MNPs and Pt(L2)/MNPs were identified using FT-IR, PXRD, SEM, TEM, EDX, and UV-spectroscopy. In vitro cytotoxicity tests on these compounds against MCF-7 cell line is applied. Additionally, the antimicrobial activity against two gram + ve bacteria (Bacillus subtilis and staphylococcus aureus), and two gram −ve bacterial strains (Escherichia coli and Salmonella typhi) was investigated. Furthermore, the antioxidant properties (DPPH) of the investigated compounds were assessed. The results of the study indicated that the [Pt(HL2)(H2O)2].Cl complex exhibited a higher biological potency compared to both the [Pt(HL1)(H2O)2].Cl complex and their respective ligands. When Pt(II) complexes were incorporated into the MNPs, a significant increase in their biological activity was noted, especially for Pt(L2)/MNPs, which exhibited the strongest antibacterial and anticancer effects.

In Vitro Antitumor, Antioxidant, and Hemolytic Activities of Chlorella sorokiniana Methanol Extracts and Collective Fractions

Chlorella species are fast-growing microalgae with significant industrial applications. The aim of the present study was to investigate the antitumor, antioxidant, and hemolytic activities of Chlorella sorokiniana UTEX 1230 crude methanol extracts and fractions. Ch. sorokiniana crude methanol extracts and collective fractions (CFs) were obtained from lyophilized biomass by maceration and column chromatography. Antitumor assays against murine lymphoma L5178Y-R and human breast cancer MCF-7 cells were performed by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction technique, using human peripheral blood mononuclear cells (PBMC) as the control group. Antioxidant and hemolytic activities were evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH) and erythrocyte hemolysis, respectively. We showed that crude methanol extracts (IC50) increased L5178Y-R and MCF-7 cell growth inhibition, without affecting PBMC. In addition, all evaluated CFs showed significantly higher antioxidant activity than the positive control (ascorbic acid). CF3 and CF4 showed the highest cytotoxicity against L5178Y-R, whereas CF3, CF4, and CF5 caused the highest antitumor activity against MCF-7 cells. CF3, CF4, and CF5 induced significantly higher hemolytic activity compared with all other fractions. CF characterization revealed loliolide, cinnamic acid, methyl dihydrojasmonate, salsalvamide A, 1-monolinolenin, cryptophycin 29, costunolide, riboflavin lumicrome, and germicidin B, which have been related to antitumor and antioxidant activities. In conclusion, we demonstrated that Ch. sorokiniana extracts and fractions possess antitumor and antioxidant potential, without affecting human erythrocytes and PBMC.

Phytochemical characterization and biomedical potential of Iris kashmiriana flower extracts: a promising source of natural antioxidants and cytotoxic agents.

Iris kashmiriana belongs to the family Iridaceae and is an important endemic medicinal plant of Kashmir. The current study was designed to determine the phytoconstituents, antioxidant, and cytotoxic potential of ethyl acetate (IRK-ETH) and methanol (IRK-MTH) extracts of Iris kashmiriana flowers. IRK-MTH extract demonstrated maximum radical scavenging activity in DPPH, ABTS, and Superoxide anion radical antioxidant assays with IC50 values of 73.15μg/ml, 79.05μg/ml, and 86.52μg/ml respectively. IRK-ETH and IRK-MTH extracts possessed phenolic (70.9 and 208.5 mgGAE/gdw) and flavonoid (487.7 and 40.55mgRE/gdw) contents respectively. In MTT assay IRK-ETH demonstrated the highest cytotoxicity towards the MCF-7 cell line with a GI50 value of 49.13μg/ml. Phase contrast and fluorescence microscopic studies in MCF-7 cells revealed that IRK-ETH extract caused condensation of chromatin, rounding of cells, and nuclear condensation in cells which shows the apoptotic potential of the extract. GCMS analysis for phytochemical characterization revealed the presence of 9 compounds in both extracts which have been reported to possess antibacterial, cytotoxic, and anti-oxidant activities. HPLC analysis confirmed the presence of different polyphenols in both extracts with IRK-MTH extract having maximum polyphenols like epicatechin, rutin, quercetin, vanillic acid, sinapic acid, caffeic acid, chlorogenic acid and ellagic acid. These findings suggest that the flowers of Iris kashmiriana possess very good antioxidant and cytotoxic potential owing to its rich phytoconstituents.

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

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

Evaluation Secondary Metabolite Extract Produced by Aspergillus terreus Isolated from Poultry Droppings as Anticancer Agent

Malignant diseases are considered one of the problems of our time, and cancer is defined as the abnormal growth of malignant cells. It is widely accepted as the leading cause of death. There is currently no proven cancer cure. As a result, scientists have concentrated on creating secure and efficient therapies. Research has been done on the effects of naturally occurring substances that have been extracted from living things, such fungus on cancer cells. This study sought to determine the natural products' efficacy against human cancer cell line MCF-7. After A. terreus was isolated from samples of chicken droppings, it was grown on potato and Sabouraud Dextrose Agars (SDA and PDA) with chloramphenicol media. It was then identified using the extracted genomic DNA, the internal transcribed spacer (ITS) region was amplified and sequenced. After 30 days of incubation at 27°C, natural metabolite products were also recovered from the fermentation medium using the ethyl acetate extraction technique. The effectiveness of the fungal extract against the human cancer cell line MCF-7 and the normal human cell line NHF cell was also determined after incubation for 27 hours with the natural extract. The treated human cancer cell line MCF-7 showed decrease of proliferation, whereas the normal human cell line NHF showed no effect. Significant inhibitor compared to cancer line. The IC50 values for MCF-7 cell lines and NHF normal human cell lines were 7.672 and 1431 μg/mL, respectively. In summary, MCF-7 was affected by the natural extract extracted from A. terreus, in contrast to the control. When these results were combined, they showed that the fungal extract is an effective anti-cancer treatment.

Different Doxorubicin Sensitivity Across Various Human Cancer Cell Lines

Doxorubicin (Dox) is a highly potent chemotherapeutic agent, approved by FDA since 1974, for treating a broad spectrum of cancers. However, development of severe side effects and drug resistance are main issues that limit the clinical use of Dox. Herein, we aimed to investigate the sensitivity of Dox in a variety of human cancer cell lines. Eleven cell lines were tested in this study including 2 hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7), 4 bladder cancer (BlCa) cell lines (UMUC-3, VMCUB-1, TCCSUP and BFTC-905), a lung cancer cell line (A549), a cervical carcinoma cell line (HeLa), a breast cancer cell line (MCF-7), a skin melanoma cell line (M21) and a noncancer human kidney cell line (HK-2). The MTT assay was employed for the determination of cytotoxicity. Cells were treated with various concentrations of Dox for 24 h. The half-maximal inhibitory concentration (IC50) of Dox was calculated to compare the Dox sensitivity among tested cell lines. The result showed that IC50 of Dox in HepG2, Huh7, UMUC-3, VMCUB-1, TCCSUP, BFTC-905, A549, HeLa, MCF-7, M21 and HK-2 cells were 12.2, &gt; 20, 5.1, &gt; 20, 12.6, 2.3, &gt; 20, 2.9, 2.5, 2.8 and &gt; 20 mM, respectively. BFTC-905 had the lowest IC50 value, therefore, it was the most sensitive to Dox. In contrast, Huh7, VMCUB-1 and A549 cells were resistant to Dox with IC50 values &gt; 20 mM. Conclusions, we demonstrated that different human malignant cell lines had different sensitivity to Dox. BFTC-905 BlCa cell line had the highest sensitivity to Dox. Huh7, VMCUB-1 and A549 cell lines were resistant to Dox. Perhaps, the different Dox sensitivity in different cell lines was due to the different acquisition of Dox resistance mechanisms. Huh7, VMCUB-1 and A549 cell lines could be suitable cell models to investigate the molecular mechanism of Dox resistance in different cancers. HIGHLIGHTS Different types of cancer cell lines exhibited different sensitivity to doxorubicin. BFTC-905, MCF-7 and M21 cell lines were sensitive to doxorubicin. HepG2, UMUC-3, TCCSUP and HeLa cells were moderately sensitive to doxorubicin. Huh7, VMCUB-1, A549 and HK-2 cells were resistant to doxorubicin. Huh7, VMCUB-1 and A549 cell lines could be suitable cell models for investigating the molecular pathways of Dox resistance in different types of cancers. GRAPHICAL ABSTRACT