SKOV3 Cell Lines Research Articles

Olaparib Combined with DDR Inhibitors Effectively Prevents EMT and Affects miRNA Regulation in TP53-Mutated Epithelial Ovarian Cancer Cell Lines

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial–mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and migratory capabilities, often driven by changing miRNA expression involved in the regulation of pathological processes like drug resistance. Targeted therapies like PARP inhibitors (PARPi) have improved outcomes, particularly in BRCA-mutated and DNA repair-deficient tumors; however, resistance and limited efficacy in advanced stages remain challenges. Recent studies highlight the potential synergy of PARPi with DNA damage response (DDR) inhibitors, such as ATR and CHK1 inhibitors, which disrupt cancer cell survival pathways under stress. This study investigated the combined effects of olaparib with ATR and CHK1 inhibitors (ATRi and CHK1i) on migration, invasion, and EMT-related protein expression and miRNA expression in ovarian cancer cell lines OV-90 and SKOV-3. The results demonstrated enhanced cytotoxicity, inhibition of migration and invasion, and modulation of miRNAs linked to metastasis. These findings suggest that combination therapies targeting DNA repair and cell cycle pathways may offer a novel, more effective approach to managing advanced EOC and reducing metastatic spread.

Synthesis and antiproliferative evaluation of novel chrysin selenocyanates

Selenocyano fragments with distinct structural characteristics were successfully incorporated into the 5- and 7-positions of chrysin via etherification and esterification of its hydroxyl groups. Eleven novel chrysin selenocyanates were synthesized, and their structures characterized by NMR and HRMS. The activities of all compounds were evaluated against human cervical cancer cell lines HeLa, ovarian cancer cell lines SKOV-3, and breast carcinoma cell lines MCF-7 using MTT assays. Results indicated that esterified chrysin derivatives significantly inhibited HeLa cells, while alkylated chrysin ethers showed notable activity against SKOV-3 and MCF-7 cells. Compounds 5c and 5e exhibited the strongest inhibitory effects on SKOV-3 cells, with IC50 values of 2.27 ± 0.19 μM and 2.51 ± 0.33 μM, respectively. The introduction of diselenocyanate at both the 5- and 7-positions demonstrated superior inhibitory activity compared to a single selenocyanate at the 7-position alone. The findings may aid in designing novel chemotherapeutic drugs.

Obacunone regulates ferroptosis in ovarian cancer through the Akt/p53 pathway.

Ovarian cancer is characterized by a high rate of recurrence and a poor prognosis. Ferroptosis, a programmed cell death that is dependent on iron and lipid peroxidation, has emerged as a novel therapeutic target in recent years. This study investigated the effects of Obacunone, a naturally occurring compound present in citrus fruits, on the induction of ferroptosis in ovarian cancer via the Akt/p53 signaling pathway. SKOV3 and OVCAR3 ovarian cancer cell lines were utilized in vitro, while a BALB/c nude mouse model was employed for in vivo experiments. Cell proliferation was assessed utilizing the CCK-8 assay and EDU incorporation. The western blot technique was employed to assess the expression levels of proteins associated with the Akt/p53 signaling pathway. The ferroptosis inhibitor Fer-1 and the Akt activator SC79 were utilized to investigate the potential mechanism of action of Obacunone. Obacunone significantly inhibited the proliferation of ovarian cancer cells and induced ferroptosis, as evidenced by increased intracellular iron content, elevated lipid peroxidation levels, and abnormal mitochondrial morphology. Obacunone also decreased GSH levels, inhibited GPX4 expression and up-regulated ACSL4, as well as reduced Akt phosphorylation and enhanced p53 expression. In vivo experiments showed that Obacunone effectively inhibited tumor growth. Obacunone exhibits potential therapeutic significance through the modulation of the Akt/p53 signaling pathway, which may induce ferroptosis and inhibit the proliferation of ovarian cancer cells.

Establishment of Novel High-Grade Serous Ovarian Carcinoma Cell Line OVAR79.

High-grade serous ovarian carcinoma (HGSOC) remains the most common and deadly form of ovarian cancer. However, available cell lines usually fail to appropriately represent its complex molecular and histological features. To overcome this drawback, we established OVAR79, a new cell line derived from the ascitic fluid of a patient with a diagnosis of HGSOC, which adds a unique set of properties to the study of ovarian cancer. In contrast to the common models, OVAR79 expresses TP53 without the common hotspot mutations and harbors the rare combination of mutations in both PIK3CA and PTEN genes, together with high-grade chromosomal instability with multiple gains and losses. These features, together with the high proliferation rate, ease of cultivation, and exceptional transfection efficiency of OVAR79, make it a readily available and versatile tool for various studies in the laboratory. We extensively characterized its growth, migration, and sensitivity to platinum- and taxane-based treatments in comparison with the commonly used SKOV3 and OVCAR3 ovarian cell lines. In summary, OVAR79 is an excellent addition for basic and translational ovarian cancer research and offers new insights into the biology of HGSOC.

Synthesis of New 1,4-Naphthoquinone Fluorosulfate Derivatives and the Study of Their Biological and Electrochemical Properties.

This study presents the synthesis of new fluorosulfate derivatives of 1,4-naphthoquinone by the SuFEx reaction. Anticancer properties of obtained compounds were studied on PC-3 (prostate adenocarcinoma), SKOV-3 (ovarian cancer), MCF-7 (breast cancer), and Jurkat cell lines. All the studied compounds showed higher cytotoxic effects than Cisplatin. The DFT method was applied to determine the electronic structure characteristics of 1,4-naphthoquinone derivatives associated with cytotoxicity. A method of determination of 2,3-dichloro-1,4-naphthoquinone (NQ), 3-chloro-2-((4-hydroxyphenylamino)-1,4-naphthoquinone (NQ1), and 4-((3-chloro-1,4-naphthoquinon-2-yl)amino)phenyl fluorosulfate (NQS) in a pharmaceutical substance using an impregnated graphite electrode (IMGE) was developed. The morphology of the IMGE surface was studied using scanning electron microscopy (SEM). The electrochemical behavior of NQ, NQ1, and NQS was studied by cyclic voltammetry (CV) in 0.1 M NaClO4 (96% ethanol solution) at pH 4.0 in a potential range from -1 to +1.2 V. Electrochemical redox mechanisms for the investigated compounds were proposed based on the determining main features of the electrochemical processes. Calibration curves were obtained by linear scan voltammetry in the first derivative mode (LSVFD) with the detection limit (LOD) 7.2 × 10-6 mol·L-1 for NQ, 8 × 10-7 mol·L-1 for NQ1, and 8.6 × 10-8 mol·L-1 for NQS, respectively.

Identification of three subtypes of ovarian cancer and construction of prognostic models based on immune-related genes

BackgroundImmunotherapy has revolutionized the treatment of ovarian cancer (OC), but different immune microenvironments often constrain the efficacy of immunotherapeutic interventions. Therefore, there is an imperative to delineate novel immune subtypes for development of efficacious immunotherapeutic strategies.MethodsThe immune subtypes of OC were identified by consensus cluster analysis. The differences in clinical features, genetic mutations, mRNA stemness (mRNAsi) and immune microenvironments were analyzed among subtypes. Subsequently, prognostic risk models were constructed based on differentially expressed genes (DEGs) of the immune subtypes using weighted correlation network analysis.ResultsOC patients were classified into three immune subtypes with distinct survival rates and clinical features. Different subtypes exhibited varying tumor mutation burdens, homologous recombination deficiencies, and mRNAsi levels. Significant differences were observed among immune subtypes in terms of immune checkpoint expression and immunogenic cell death. Prognostic risk models were validated as independent prognostic factors demonstrated great predictive performance for survival of OC patients.ConclusionIn this study, three distinct immune subtypes were identified based on gene sets related to vaccine response, with the C2 subtype exhibiting significantly worse prognosis. While no statistically significant differences in tumor mutation burden (TMB) were observed across the three subtypes, the homologous recombination deficiency (HRD) score and mRNA stemness index (mRNAsi) were notably elevated in the C2 group compared to the others. Immune infiltration analysis indicated that the C2 subtype may have an increased presence of regulatory T (Treg) cells, potentially contributing to a more favorable response to combination therapies involving PARP inhibitors and immunotherapy. These findings offer a precision medicine approach for tailoring immunotherapy in ovarian cancer patients. Moreover, the C3 subtype demonstrated significantly lower expression levels of immune checkpoint genes, a pattern validated by independent datasets, and associated with a better prognosis. Further investigation revealed that the immune-related gene FCRL5 correlates with ovarian cancer prognosis, with in vitro experiments showing that it influences the proliferation and migration of the ovarian cancer cell line SKOV3.

Fine-tuning the cytotoxicity profile of N,N,N-trimethyl chitosan through trimethylation, molecular weight, and polyelectrolyte complex nanoparticles

N,N,N-trimethyl chitosan (TMC) is a promising biopolymer for pharmaceutical applications due to its enhanced solubility and bioadhesive properties, though its cytotoxic limitations necessitate careful modification to ensure safety and efficacy. This study sought to investigate whether nanoparticle (NP) formation could reduce the anticipated cytotoxic effects of TMC, thus improving its applicability across a wider spectrum of pharmaceutical uses. TMC's capability to form NPs with anionic polyelectrolytes led to the application of chondroitin sulfate (ChS) in this study. Five TMC samples, varying in degree of trimethylation (DTM 23, 32, 46, 50 and 99 %) and molecular weight (Mw, 66–290 kDa) were synthesized, and their biocompatibility with human umbilical vein endothelial cells (HUVECs) was assessed. The results revealed a discernible impact of both DTM and Mw on cell viability, with higher DTM and lower Mw correlating with increased toxicity. Cytotoxicity studies against ovarian cancer cell lines SKOV-3 and OVISE showed a clear indication of a higher cytotoxic effect of TMC samples against cancer cells compared to healthy cells (HUVEC). The cytotoxicity against cancer cells also indicated an optimal DTM for maximum efficacy, deviating from a linear trend. The effects of Mw were cell-dependent, introducing complexity to the observed relationship. Additionally, TMC-ChS NPs were successfully prepared, demonstrating a substantial reduction in cytotoxicity compared to TMC alone in all tested cells. This promising outcome suggests the potential of NP formation to fine-tune the cytotoxicity profile of TMC, paving the way for the development of safer and more effective pharmaceutical formulations.

Assessing functional suitability of a lyophilized formulation containing designed ankyrin repeat proteins for radionuclide imaging of HER2/neu overexpression in malignant tumors

Aim. To study in vitro and in vivo the functional suitability of 99mTc-labeled lyophilized formulation containing designed ankyrin repeat protein (DARPin) G3-(GGGS)3Cys for radionuclide imaging of HER2/neu overexpression in malignant tumors.Materials and methods. To create a targeted protein, a modified genetic construct with the sequence encoding DARPin G3-(GGGS)3Cys was used. To generate the experimental probe, we used a lyophilized formulation containing DARPin G3-(GGGS)3Cys with auxiliary substances and 99mTc sodium pertechnetate (500 MBq) incubated at 60 °C for 30 min. Radiochemical purity of 99mTc-G3-(GGGS)3Cys was analyzed by thin-layer radiochromatography. SKOV-3, BT-474, and DU-145 cell lines were used to test binding specificity in vitro. The dissociation constant was determined via a saturation binding assay on SKOV-3 cells with a range of protein concentrations from 0.2 to 40 nM. Nu/j mice bearing HER2-positive SKOV-3 xenografts and HER2-negative Ramos xenografts were used to evaluate the targeting properties and biodistribution.Results. A radiocomplex based on 99mTc and a lyophilized formulation with DARPin G3-(GGGS)3Cys was obtained with the radiochemical purity of more than 96%. Binding of 99mTc-G3-(GGGS)3Cys to the cells was specific (KD 3.9 ± 0.5 nM) and proportional to the level of HER2/neu expression in the cells. The uptake of 99mTc-G3-(GGGS)3Cys in SKOV-3 xenografts was significantly higher than in Ramos xenografts. 99mTc-G3-(GGGS)3Cys demonstrated rapid blood and renal clearance and had low activity in the salivary glands and stomach. Liver uptake was about 5–7%ID/g. In addition, 99mTc-G3-(GGGS)3Cys exhibited very low uptakes in the lungs, muscles, small intestine, and bones.Conclusion. The 99mTc-labeled lyophilized formulation with DARPin G3-(GGGS)3Cys is functionally suitable for imaging HER2/neu overexpression in tumors, as it binds specifically to the receptor, is stable in vivo, and has favorable biodistribution in organs and tissues. The radiocomplex based on 99mTc-G3-(GGGS)3Cys was obtained by a simple method with high radiochemical purity.

Heteroleptic complexes of hydrazone Scaffold of picolinoyl N- oxide and 2,4 dihydroxy phenyl moieties; evaluation of antioxidant activity, DNA and protein binding properties and in vitro antiproliferation studies

The present study deals with design and synthesis of new mononuclear Cu(II), Co(II), Ni(II) and Zn(II) metal complexes of hydrazone of 2-(2-(2,4-dihydroxybenzylidene)hydrazinecarbonyl)pyridine-1-oxide (H2L), in a view to study their potential relevance for the biological applications. Structural aspects of the title compound (H2L) and metal complexes synthesized were evaluated by spectral and analytical methods viz. 1H NMR, 13C NMR, LC-MS, FT-IR, UV–Visible, SEM, EDX, Powder XRD, ESR, TGA and DTA. Ligational properties of H2L were explored by employing pH metric equilibrium studies for recognizing metal ion binding potential donor sites, and further HyperChem 7.5 software for computing properties of frontier molecular orbitals to ascertain orientation of highest occupied molecular orbitals from which presumably electrons are donated to metal ion in complex formation. The affinity of all title compounds to bind with CT-DNA and the type of interaction, therein have been studied by conducting UV–VIS absorption and fluorescence emission titrations. The protein-binding ability of all metal complexes with two serum proteins (BSA and HSA) were explored by absorption titrations, and further fluorescence titrations for BSA binding were also performed. Antioxidant activity of the title compounds was carried out by the method of free radical scavenging using spectrophotometric technique. Additionally, cytotoxicity of all metal complexes and ligand was measured by CTG cell proliferation assay after treating them with MDA-MB-231 and SKOV-3 cell lines. The cell cycle arrest and apoptosis assay in above cell lines after treatment with title compounds were also investigated by flow cytometry. In addition, molecular docking studies at target CDK2 protein inferred binding affinity of the title compounds through non covalent bonding interactions.

Cationic Polystyrene Latex Nanocarriers for Immunostimulatory Long Double-Stranded RNA Delivery to Ovarian Cancer Cells.

Long double-stranded (ds)RNA, a potent stimulator of type I interferon and the innate immune response. In the present study, we demonstrated, for the first time, the efficacy of cationic polystyrene latex nanostructures (clNPs) as a dsRNA carrier, improving cellular delivery and robustly potentiating the immunostimulatory capacity of dsRNA in the ovarian cancer cell line SKOV3. The clNPs complexed with an in vitro transcribed dsRNA molecule, were bound by SKOV3 cells, and had increased cellular association compared to uncomplexed clNPs. clNPs complexed with dsRNA induced a more robust innate immune response compared to dsRNA alone. Transcript expression of two interferon-stimulated genes, were increased 47- and 108-fold over dsRNA and induced a significant antiviral state against vesicular-stomatitis virus, resulting in a 3.3-fold improvement on the efficacy of dsRNA. These data highlight the potential of polystyrene latex nanostructures as dsRNA carriers for anticancer immunotherapies, improving the uptake and efficacy of the nucleic acid.

Transcriptome analysis of the effect of HERV-K env gene knockout in ovarian cancer cell lines.

Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of various diseases, particularly cancers. Previous investigations from our group demonstrated that targeted knockout (KO) of the HERV-K env gene led to a significant reduction in tumorigenic attributes, including proliferation, migration, and invasion of ovarian cancer cells. In this study, we aimed to elucidate the impact of HERV-K env KO on gene expression in ovarian cancer cell lines through comparative RNA sequencing (RNA-Seq) analysis with two distinct HERV-K env KO ovarian cancer cell lines, SKOV3 and OVCAR3. HERV-K env gene KO was achieved in SKOV3 and OVCAR3 ovarian cancer cell lines using the CRISPR-Cas9 system. Next-generation mRNA sequencing was employed to assess the gene expression profiles of both mock and HERV-K env KO ovarian cancer cells. Furthermore, comprehensive analyses involving gene ontology and pathway assessments were conducted. Transcriptome analysis revealed that 23 differentially expressed genes (DEGs) were upregulated and 17 DEGs were downregulated in SKOV3 cells. In OVCAR3 cells, 198 DEGs were upregulated, and 17 DEGs were downregulated. Notably, 53 DEGs exhibited statistically significant differences among the 1,612 DEGs identified. Our findings indicate that HERV-K env gene KO exerts a profound influence on gene expression patterns in OVCAR3 cells, while genetic alterations in expression were relatively modest in SKOV3 cells. Nevertheless, genes ND1, ND2, and CYTB displayed a common increase in expression, while ERRFI1 and NDRG1 exhibited a decrease in expression in both cell lines. Our study demonstrates that KO of the HERV-K env gene in ovarian cancer cell lines has a substantial impact on gene expression patterns and can be used to identify potential therapeutic targets for ovarian cancer and related diseases.

Advancing 3D Spheroid Research through 3D Scaffolds Made by Two-Photon Polymerization.

Three-dimensional cancer cell cultures have been a valuable research model for developing new drug targets in the preclinical stage. However, there are still limitations to these in vitro models. Scaffold-based systems offer a promising approach to overcoming these challenges in cancer research. In this study, we show that two-photon polymerization (TPP)-assisted printing of scaffolds enhances 3D tumor cell culture formation without additional modifications. TPP is a perfect fit for this task, as it is an advanced 3D-printing technique combining a μm-level resolution with complete freedom in the design of the final structure. Additionally, it can use a wide array of materials, including biocompatible ones. We exploit these capabilities to fabricate scaffolds from two different biocompatible materials-PEGDA and OrmoClear. Cubic spheroid scaffolds with a more complex architecture were produced and tested. The biological evaluation showed that the human ovarian cancer cell lines SKOV3 and A2780 formed 3D cultures on printed scaffolds without a preference for the material. The gene expression evaluation showed that the A2780 cell line exhibited substantial changes in CDH1, CDH2, TWIST, COL1A1, and SMAD3 gene expression, while the SKOV3 cell line had slight changes in said gene expression. Our findings show how the scaffold architecture design impacts tumor cell culture 3D spheroid formation, especially for the A2780 cancer cell line.

Oxyresveratrol Enhances the Anti-Cancer Effect of Cisplatin against Epithelial Ovarian Cancer Cells through Suppressing the Activation of Protein Kinase B (AKT).

Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin's ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY's potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.

TNFRSF10D expression as a potential biomarker for cisplatin-induced damage and ovarian tumor relapse prediction

Among gynecological malignancies, ovarian cancer (OC) presents the most challenging diagnostic scenario. Despite exhaustive efforts, up to 90 % of patients treated with taxane/platinum-based chemotherapy experience relapse, leading to poor survival rates. Identifying new molecular markers that can characterize disease aggressiveness, chemoresistance, recurrence risk, and metastasis is crucial. This study aimed to assess the susceptibility of three ovarian tumor cell lines (TOV-21G, SKOV-3, and OV-90) to cisplatin and paclitaxel, and to investigate the influence of these treatments on the mRNA expression of TANK, RIPK1, NFKB1, TNFRSF10D, and TRAF2. Among the cell lines, SKOV-3 ovarian adenocarcinoma cells demonstrated the highest resistance to cisplatin treatment (0.125 mg/mL), followed by TOV-21G (0.076 mg/mL) and OV-90 cells (0.028 mg/mL). Regarding paclitaxel treatment, the SKOV-3 cell line exhibited the highest resistance (1.4 µg/mL), followed by OV-90 (1.3 µg/mL) and TOV-21G cells (0.9 µg/mL). Gene expression analysis after paclitaxel treatment remained unchanged; however, after cisplatin treatment, TNFRSF10D was observed to be upregulated nearly 100-fold in SKOV-3 compared to all other cell lines studied. SKOV-3 is described as cisplatin and tumor necrosis factor-resistant. Despite the defective signaling of the TNFRSF10D receptor for apoptosis, it can activate the NFKB transcription factor through non-canonical TRAIL signaling, contributing to a pro-inflammatory immune response. In light of this, damage associated with cisplatin increases TNFRSF10D expression and may promote cell survival through non-canonical NFKB pathway activation. This suggests that resistance to TRAIL-induced apoptosis in these cells could serve as a promising chemoresistance biomarker in OC.

Synthesis, crystal structure, DNA/protein interactions and cytotoxicity studies of tridentate ligand based Cu(II) complexes with various amine co-ligands

The present study utilizes a tridentate ligand H2L (1) derived as a condensation product of dehydroacetic acid and 2-furoic acid hydrazide for the synthesis of a series of copper complexes, namely [Cu(L)(bipy)] (3), [Cu(L)(4,4′-Me2-bipy)] (4), [Cu(L)(6,6′-Me2-bipy)] (5), [Cu(L)(phen)] (6), [Cu(L)(2,9-Me2-phen)] (7) [Cu(L)(pyrazino[2,3]phen)] (8) [Cu(L)(2,2′-dipyridylamine)] (9) [Cu(L)(diphenylmethanamine)] (10), obtained by reacting Cu(acetate)2 with the doubly deprotonated ligand and a range of co-ligand amines. All the synthesized compounds were fully structurally characterized using IR, 1H NMR, HRMS and single-crystal X-ray diffraction studies. The thermal stability and decomposition pattern was investigated using TGA studies. The bio-efficacy of the developed ligand and its complexes was evaluated in anti-cancer assay against SKOV3 cell lines. Copper complexes have been extensively studied for their potential to generate anticancer properties. Most complexes comprise mixed ligands, such as N-N-chelating heterocycles like 2,2’-bipyridine (bpy) and 1,10 phenanthroline (phen), chosen for their chelating and intercalative characteristics. Complex 7 displayed the highest anti-cancer activity with an IC50 value of 0.8 µM compared to standard drug doxorubicin. The impact of complex 7 on DNA fragmentation was also assessed through agarose gel electrophoresis, which indicated that complex 7 promotes observable DNA fragmentation. The serum binding affinity of the complex 7 was also investigated against BSA and HSA protein. The strong binding affinity of complex [Cu(L)(2,9-Me2-phen)] (7) with BSA/HSA and its better stability compared to the other investigated complexes were deduced based on its biological activity. The impact of varying concentrations of complex 7 on BSA and HSA was investigated using absorption spectroscopy, revealing the presence of a dynamic quenching mechanism. In silico molecular dynamics and docking, approaches have been utilized to validate the empirical data derived from serum binding studies.

Antitumor Activity of Dehydroxymethylepoxyquinomicin (DHMEQ) in Monotherapy and Combination with Cisplatin in the SKOV-3 Ovarian Cancer Model

The objective of this study was to evaluate the antitumor activity of DHMEQ as monotherapy and in combination with cisplatin in a human ovarian cancer xenograft model. Cisplatin was used as a comparator. To create the xenograft model, human ovarian cancer cells (SKOV-3 line) were subcutaneously implanted into immunodeficient mice. The study was conducted on female SCID Beige C.B-17 Cg-Prkdcscid Lystbg/Crl mice. Antitumor activity was determined by comparing tumor growth inhibition (TGI) in the treatment groups to that in the control group. Results showed that daily intraperitoneal administration of DHMEQ at a dose of 14 mg/kg following a single intraperitoneal dose of cisplatin at 4 mg/kg reduced tumor growth in the SKOV-3 cell line xenograft model.

Deciphering the effect of Potentilla fulgens root extract against healthy HUVEC cell line and cancer cell lines (A549 and SKOV-3)

BackgroundPotentilla fulgens, a highly valued indigenous medicinal herb grown in high altitudes of the Himalayan region with anticancer, hypoglycaemic, antibacterial, anti-inflammatory, and antiulcerogenic properties, are used in traditional systems of medicine. This study was aimed to investigate the effect of P. fulgens root extract, as one of the natural alternatives to chemotherapeutic drugs used in cancer treatment, on proliferation, apoptosis, and autophagy of human non-small cell lung cancer cell line (A549), human ovarian cancer cell line (SKOV-3), and healthy human umbilical vein endothelial cell line (HUVEC). MethodsAnti-proliferative effect was assessed by MTT assay. The expression of autophagy and apoptosis-related proteins was evaluated by western blotting. Total oxidant status (TOS) and total antioxidant capacity (TAC) test were determined using standard kit methods. ResultsOur results showed that the extract inhibited proliferation of HUVEC, A549, and SKOV-3 cells in a dose-dependent manner. MTT assay analysis revealed that the extract significantly (P<0.05) induced mortality in HUVEC, A549, and SKOV-3 cells. Western blot results revealed increased expression of NF-κB after the extract treatment but led to the down-regulation in Beclin-1, Bax, extracellular-signal-related kinase 1 and 2, Sequestosome-1, and cleaved Casp-3 levels. Treatment groups showed an increase in TOS and TAC values in A549 and SKOV-3 cell lines, while HUVEC cell line showed an increase in TAC and a decrease in TOS values, compared to the control group. ConclusionsOur findings indicated that P. fulgens root extract inhibited the proliferation of healthy cells and cancer cells through cell cycle arrest, representing its limited application as therapeutic agent in cancer treatment.

Panicum maximum Jacq. mediated green synthesis of silver nanoparticles: synthesis, characterization, and biological activities supported by molecular docking

This study uses the aerial parts of Panicum maximum total extract (PMTE) to synthesize silver nanoparticles (AgNPs) in an environmentally friendly manner. TEM, SEM, FTIR, X-ray powder diffraction (XRD), Zeta potential, UV, and FTIR were used to characterize the green silver nanoparticles (PM-AgNPs). PM-AgNPs were evaluated as anticancer agents compared to (PMTE) against breast (MCF-7), lung (A549), and ovary adenocarcinoma (SKOV3) human tumour cells. The antibacterial activity of AgNPs was assessed against Staphylococcus aureus isolates. The PM-AgNPs had an absorbance of 418 nm, particle size of 15.18 nm, and zeta potential of −22.4 mV, ensuring the nanosilver’s stability. XRD evaluated the crystallography nature of the formed PM-AgNPs. The cytotoxic properties of PM-AgNPs on MCF-7 and SKOV 3 were the strongest, with IC50s of 0.13 ± 0.015 and 3.5 ± 0.5 g/ml, respectively, as compared to A549 (13 ± 3.2 µg/mL). The increase in the apoptotic cells was 97.79 ± 1.61 and 96.6 ± 1.91% for MCF-7 and SKOV3 cell lines, respectively. PM-AgNPs were found to affect the membrane integrity and membrane permeability of 50 and 43.75% of the tested isolates, respectively. Also, PM-AgNPs have recorded a reduction in the biofilm formation of S. aurues. These results suggest using PM-AgNPs to treat breast and ovarian cancers.

Comprehensive analysis of hub genes associated with cisplatin-resistance in ovarian cancer and screening of therapeutic drugs through bioinformatics and experimental validation

BackgroundTo identify key genes associated with cisplatin resistance in ovarian cancer, a comprehensive analysis was conducted on three datasets from the GEO database and through experimental validation.MethodsGene expression profiles were retrieved from the GEO database. DEGs were identified by comparing gene expression profiles between cisplatin-sensitive and resistant ovarian cancer cell lines. The identified genes were further subjected to GO, KEGG, and PPI network analysis. Potential inhibitors of key genes were identified through methods such as LibDock nuclear molecular docking. In vitro assays and RT-qPCR were performed to assess the expression levels of key genes in ovarian cancer cell lines. The sensitivity of cells to chemotherapy and proliferation of key gene knockout cells were evaluated through CCK8 and Clonogenic assays.ResultsResults showed that 12 genes influenced the chemosensitivity of the ovarian cancer cell line SKOV3, and 9 genes were associated with the prognosis and survival outcomes of ovarian cancer patients. RT-qPCR results revealed NDRG1, CYBRD1, MT2A, CNIH3, DPYSL3, and CARMIL1 were upregulated, whereas ERBB4, ANK3, B2M, LRRTM4, EYA4, and SLIT2 were downregulated in cisplatin-resistant cell lines. NDRG1, CYBRD1, and DPYSL3 knock-down significantly inhibited the proliferation of cisplatin-resistant cell line SKOV3. Finally, photofrin, a small-molecule compound targeting CYBRD1, was identified.ConclusionThis study reveals changes in the expression level of some genes associated with cisplatin-resistant ovarian cancer. In addition, a new small molecule compound was identified for the treatment of cisplatin-resistant ovarian cancer.

Regulation of cancer cell ferroptosis by PTRF/Cavin-1

Ovarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cells to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress, and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.