Search Results (608)

Although Simarouba glauca DC. has been recognized for its therapeutic properties, its anticancer effects against oral cancer have not been adequately investigated. The present study aimed to evaluate the activity of S. glauca leaf extracts against oral squamous cell carcinoma (OSCC). S. glauca leaves were extracted using solvents of increasing polarity, and the resulting fractions were evaluated for their phytochemical composition, antioxidant activity, and cytotoxic effects. Among all extracts, the S. glauca hexane extract (SGHE) exhibited the most potent anticancer activity against cell lines representing OSCC (CAL-27), cervical cancer (HeLa), and mouse mammary tumors (4T1). Bioactivity-guided fractionation identified D-erythro-Sphinganine as a major constituent present in hexane extract, possibly contributing to anticancer activity. But since the anticancer activity of crude hexane extract is superior compared to isolated D-erythro-Sphinganine, we predict a synergistic interaction among the multiple bioactive compounds present in the crude hexane extract. Hence, further studies were carried out with crude hexane extract. Mechanistic studies have shown that the anticancer activity of hexane extract is due to its ability to (a) alter cell cycle progression, (b) trigger apoptosis, and (c) inhibit cell migration in CAL-27 cells. Overall, these findings indicate that the hexane extract of S. glauca leaf possesses multi-target anticancer potential and warrants further mechanistic and in vivo investigations. Full article

This study reports the exclusive and rapid synthesis of twenty-four derivatives of 1-((mono/bis)trifluoromethyl)phenyl-3-(4-arylthiazol-2-yl)thioureas (series 7, 9 and 11), along with their antimicrobial activities against Candida albicans, Mycobacterium smegmatis and seven additional bacterial strains. The anticancer potential of these compounds was evaluated against various human cancer cell lines, including A549 (lung adenocarcinoma), HeLa (cervical carcinoma), IMR32 (neuroblastoma), MCF-7 (breast adenocarcinoma), HCT116 (colon cancer) and DU145 (prostate cancer). Among these, 1-(3,5-bistrifluoromethylphenyl)-3-(thiazol-2-yl)thiourea (7i) and 1-(4-trifluoromethylphenyl)-3-(4-(3-chlorophenyl)thiazol-2-yl)thiourea (11h) demonstrated significant antimicrobial activity against M. luteus, S. aureus, S. aureus 1 and C. albicans. Additionally, 1-(4-(3-chlorophenyl)thiazol-2-yl)-3-(3-trifluoromethylphenyl)thiourea (9g) and 1-(4-trifluoromethylphenyl)-3-(4-(2-fluorophenyl)thiazol-2-yl)thiourea (11g) showed activity against Mycobacterium smegmatis. The bioassay tests indicated that many of the thiourea derivatives exhibited moderate activity against the A549, HeLa, MCF-7 and HCT116 cancer cell lines. Full article

Cervical cancer (CC) remains a significant public health problem. Despite the availability of standard treatment strategies, chemotherapy-resistant tumors persist, highlighting the need to explore new therapeutic approaches or adjuvant strategies. This underscores the importance of preclinical in vivo models. Conventional models, such as murine xenografts, patient-derived xenografts (PDXs), and patient-derived organoids (PDOs), provide valuable biological relevance but are often time-consuming, costly, and resource-intensive. In this context, the chick embryo chorioallantoic membrane (CAM) assay represents a rapid, low-cost, and technically accessible in vivo platform. The CAM is a non-innervated, highly vascularized extraembryonic structure that provides a suitable environment for tumor generation from xenografts. However, despite the broad use of the CAM assay for tumor xenografts, standardized and comparative methodological optimizations specifically addressing technical variables for cervical cancer tumor induction remain limited. Therefore, the aim of this study was to optimize the CAM assay for tumor generation using the HeLa and SiHa cell lines. The generated tumors are vascularized and exhibit Ki-67 expression. The CAM assay is an excellent short-term exploratory model based on developing chicken embryos for studying the developmental biology of cervical tumors, which would accelerate the preclinical investigation of new therapeutic molecules. Full article

Cervical cancer remains a prominent cause of cancer-related mortality among women worldwide because of chronic infection with high-risk human papillomavirus (HPV) and disparate access to prevention and treatment. The current research evaluates the anticancer activity of Gypenoside XVII, a bioactive saponin of Gynostemma pentaphyllum, in HeLa cells as a model of cervical cancer. MTT, Annexin V-PI, and Hoechst 33342 assays showed dose-dependent growth inhibition with typical apoptotic morphology. Flow cytometry revealed G₀/G₁ cell-cycle arrest, while pathway interrogation revealed participation of mitochondrial and death-receptor cascades, in agreement with caspase-9 and caspase-8 activation, respectively. Collectively, these findings position Gypenoside XVII as a natural-product bioactive with potential both as an anticancer lead and as a functional-food ingredient, deserving of further preclinical development. Full article

Cervical cancer (CC) remains a common malignant tumor that seriously threatens women’s health globally. Gramine (GR), a natural alkaloid derived from plants such as Arundo donax L., exhibits anti-tumor activities, yet its mechanistic actions in CC are still unclear. Here, we integrated cell-based assays, network pharmacology, and multi-omics analysis to systematically investigate the molecular mechanisms underlying GR’s anti-CC effects. In vitro experiments showed that GR significantly inhibited proliferation and migration, induced apoptosis, and triggered G₀/G₁ phase cell cycle arrest in HeLa cells. Integrated multi-omics analysis identified CDK2 as a critical target of GR, with both mRNA and protein levels markedly reduced following treatment. Mechanistically, GR likely suppresses CC progression by modulating the “CYP4A22-AS1/LINC00958–hsa-miR-133b–CDK2” competitive endogenous RNA (ceRNA) axis. Immune analysis indicated positive correlations of CDK2, CYP4A22-AS1, and LINC00958 with the immune checkpoint molecule CD47. Collectively, our findings demonstrate that GR inhibits CC through a ncRNA-mediated suppression of CDK2, leading to reduced HeLa cell proliferation and migration and enhanced apoptosis. These results provide a mechanistic rationale for developing GR as a candidate agent for targeted therapy and immuno-combination strategies in CC. Full article

Background/Objectives: Long-chain fatty acids induce lipid droplet formation in several cell types including cancer cells. These lipid droplets have been shown to accumulate in various cancers and are dysregulated in many pathologies. Thus, this study was designed to examine the many unique long-chain fatty acids and their abilities to induce lipid droplet formation in cancer cells. Methods: HeLa human cervical cancer cells were incubated with individual fatty acids and live-stained for lipid droplets. This study analyzed four saturated, four monounsaturated, and nine polyunsaturated (4 omega-3, 4 omega-6, and 1 omega-9) fatty acids. This diversity of fatty acids was chosen to highlight any important non-uniform differences in the regulation of lipid droplet formation by unsaturated fatty acids. The area of the lipid droplets and the number of lipid droplets per cell were measured and compared between the different fatty acid conditions. Results: Unsaturated fatty acids induced lipid droplets differently compared to saturated fatty acids. Further, an inverse relationship was established between average area of lipid droplets and the average number of lipid droplets per cell. Finally, two perilipin genes (PLIN1/2) involved in lipid droplet formation were shown to have significantly higher expression with the two polyunsaturated fatty acids (alpha- and gamma-linolenic acid) versus the saturated fatty acid (stearic acid) condition. Conclusions: Together, different fatty acids produce structurally different lipid droplets. It will be important to further investigate the biochemistry and mechanistic differences in the formation of these lipid droplets under these specific long-chain fatty acid conditions. Full article

Background/Objectives: Research on noble metal nanoparticles (NPs) has increased over the past three decades, with advancements in synthesis techniques refining their physicochemical characteristics, including size, shape, and surface chemistry. Bimetallic NPs (BNPs) offer synergistic properties contributed by both metals. Gold (Au) and palladium (Pd) NPs possess low toxicity, high biocompatibility and loading, ease of synthesis and surface modification. Doxorubicin (DOX) and 5-fluorouracil (5-FU) are potent chemotherapeutic drugs but are rapidly metabolised in the body, producing severe side effects, limiting their use. Hence, innovative strategies to mitigate this is needed. Methods: In this study, AuPd NPs in a core-shell formation were chemically synthesized. The AuPd NPs were conjugated to 5-FU and DOX-encapsulated CS complexes and decorated with the targeting moiety transferrin (Tf). Results: Transmission electron microscopy and nanoparticle tracking analysis confirmed that the BNPs were spherical, with an average size of 73.4 nm. Functionalized BNPs were able to encapsulate more than 70% of 5-FU and DOX, resulting in a controlled drug release profile at pH 4.2. Cytotoxicity levels in human cancer cells, HeLa (cervical carcinoma) and MCF-7 (breast adenocarcinoma), as well as in non-cancer HEK293 (embryonic kidney) cells, revealed that the Tf-targeted nanocomplexes were HeLa cell-specific, with no significant cytotoxicity in the HEK293 cells. Tf-mediated cellular uptake was confirmed by receptor competition studies in the HeLa cells. Apoptosis and oxidative stress analysis confirmed cell death by apoptosis, consistent with the action of 5-FU and DOX. Conclusions: This study highlighted the potential of this BNP-nanocomplex as a suitable vehicle for drug delivery. Full article

Early detection of premalignant cervical lesions is essential for improving cervical cancer outcomes; however, current screening methods frequently lack adequate sensitivity and specificity. This research introduces a diagnostic platform that integrates lectin-based biosensors with spectral and multivariate analysis. The biosensors are composed of gold nanoparticles (AuNPs) conjugated with Maackia amurensis (MAA) lectin, which selectively binds to α2,3-linked sialic acid. Validation was performed using cervical cancer cell lines (SiHa, HeLa, C33A), fibroblasts, and cervical scrapes, and specificity was verified by enzymatic removal of sialic acids. Spectral data were obtained using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and analyzed by principal component analysis (PCA). Application of PCA to the 1600–1350 cm⁻¹ spectral region, using 99% confidence ellipses, enabled clear differentiation between samples negative and positive for intraepithelial lesions in a double-blind study of 58 patients. The MAA biosensors exhibited high sensitivity and specificity, comparable to established diagnostic methods. These results indicate that the combination of ATR-FTIR spectroscopy, MAA lectin-based biosensors, and chemometric analysis provides a robust and reliable approach for early detection of premalignant cervical lesions, with considerable potential to enhance patient outcomes. Full article

Janus kinase 2 (JAK2) is a key mediator of oncogenic signaling and a promising therapeutic target in cervical cancer. This study employed a combination of in silico and in vitro approach to discover sesquiterpene lactone (SL) derivatives with JAK2 inhibitory activity. Molecular docking of forty SL derivatives, followed by drug-likeness and toxicity prediction, led to the selection of six candidates for synthesis and biological evaluation. Among these, SL10 (12.7 nM) and SL35 (21.7 nM) demonstrated potent JAK2 inhibition and exhibited selective cytotoxicity toward HeLa cervical cancer cells, outperforming ruxolitinib. Flow cytometry confirmed apoptosis induction and ROS elevation, suggesting ROS-mediated cytotoxic mechanisms. The 1 µs MD simulations demonstrated that both hydrogen bonding and hydrophobic interactions are critical determinants in stabilizing potent SLs–JAK2 complexes. These findings support SL10 and SL35 as promising scaffolds for further development of JAK2-targeted therapies in cervical cancer. Full article

Background/Objectives: Cervical cancer remains a major global health challenge, and treatment resistance limits the long-term success of chemotherapy. Drug repurposing strategies offer new opportunities for improving therapeutic outcomes by combining existing agents with established chemotherapeutics. Sitagliptin, a DPP-4 inhibitor commonly used in type 2 diabetes, has recently gained attention for its potential anticancer effects. This study aimed to investigate the cytotoxic, apoptotic, and anti-metastatic effects of sitagliptin and doxorubicin, individually and in combination, on human cervical cancer cells (HeLa), and to determine whether their combined use exerts a synergistic anticancer effect. Methods: HeLa cells were treated for 48 h with increasing concentrations of sitagliptin, doxorubicin, or their combination. Cell viability was assessed using the MTT assay. Apoptosis was evaluated by Annexin V-FITC/PI staining and caspase-8/9 activity assays. Synergy was quantified using the Chou–Talalay method, and Combination Index (CI) values were used to determine synergistic interactions. Intracellular ROS levels were measured using the DCFDA assay. Migration and invasion capacities were analyzed using wound healing and Transwell assays. MMP-1, MMP-2, TIMP-1, and TIMP-2 levels were quantified via ELISA with normalization to viable cell counts. Gene expression levels of PI3K/Akt and MAPK/ERK pathway components were measured by qRT-PCR. Bioinformatic analyses (STRING, GeneMANIA, GO, KEGG) were performed to identify common molecular targets and enriched pathways affected by both agents. Results: The combination of sitagliptin and doxorubicin significantly reduced cell viability and demonstrated a synergistic interaction (CI < 1). Combined treatment induced a marked increase in ROS production and significantly elevated apoptosis rates compared to monotherapies. Caspase-8 and caspase-9 activities were also higher in the combination group. Migration and invasion assays revealed substantial suppression of cell motility and invasive capacity. After normalization to viable cell numbers, MMP and TIMP reductions remained significant, confirming true biological inhibition rather than cell-death–related artifacts. qRT-PCR analyses showed downregulation of Akt and ERK expression, indicating suppression of key survival and proliferation pathways. Bioinformatic analyses supported these findings by highlighting enrichment in apoptotic, oxidative stress, and metastasis-related pathways. Conclusions: Sitagliptin enhances the anticancer efficacy of doxorubicin by amplifying ROS-mediated apoptosis, inhibiting migration and invasion, and modulating PI3K/Akt and MAPK/ERK signaling in cervical cancer cells. The combination exhibits a clear synergistic effect and demonstrates strong potential as a supportive therapeutic strategy. These findings warrant further in vivo and clinical-level investigations to evaluate the translational applicability of sitagliptin in cervical cancer therapy. Full article

Developing precise tumor-targeting delivery systems while minimizing off-target toxicity continues to pose significant challenges in medicine application. The integration of two different functional materials has emerged as a promising strategy in current biomedical research. Herein, a hybrid nanocomposite consisting of Fe₃O₄ and ZnO was synthesized via a simple approach and employed as a nanoscale drug delivery system to explore the loading capacity and stimuli-responsive release characteristics of the anticancer agent doxorubicin (DOX). Results show that the synthesized nanoparticles (NPs) exhibit a multi-scale nanostructure consisting of the spindle-like ZnO nanorods with a mean length of 280 nm, on which the Fe₃O₄ NPs with a diameter of around 16 nm are uniformly dispersed. The ZnO@Fe₃O₄ NPs possess superparamagnetic behavior and a fast response to the external magnet and demonstrate exceptional near-infrared (NIR) photothermal conversion efficiency. In drug release studies, the ZnO@Fe₃O₄ NPs achieve the controlled DOX release in the simulated acidic tumor microenvironment as well as NIR laser irradiation. Further, the ZnO@Fe₃O₄-DOX composites significantly suppress the viability of human cervical cancer cells (HeLa) upon laser activation. These findings suggest that ZnO@Fe₃O₄ NPs are promising candidates for combined photothermal therapy, magnetic-targeted drug delivery, and stimuli-responsive controlled release applications. Full article

Background/Objectives: Cancer is among the leading causes of mortality worldwide. In 2022 alone, the global cancer death toll stood at 9.74 million. Projections indicate that this figure will rise to 10.4 million by 2025. Methods: A new series of benzimidazolone-bridged hybrid compounds containing thiophene, furan, oxadiazole, piperazine, and coumarin moieties was synthesized and structurally characterized by ¹H-NMR, ¹³C-NMR (APT), and elemental analysis. Their cytotoxic effects were evaluated by MTT assay against human lung (A549), human breast (MCF-7), and human cervical (HeLa) cancer cell lines, and the non-cancerous HEK293 cell line after 48 h exposure over a concentration range of 0.5–250 µM. IC₅₀ values were determined, and Selectivity Indexes (SI) were calculated using HEK293 as the reference normal cell line. Molecular docking studies were carried out using the Glide XP protocol against VEGFR2 (PDB ID: 4ASD) and CDK4–Cyclin D3 (PDB ID: 7SJ3), with sorafenib and abemaciclib as reference inhibitors. Results: The results of anticancer activity were compared with doxorubicin (IC₅₀ ± SD (µM)/SI: 4.3 ± 0.2/1.20 for A549, 6.4 ± 0.37/0.77 for MCF-7, 3.4 ± 0.19/1.54 for HeLa), a drug used for cancer chemotherapy. The structures of the newly synthesized hybrid compounds were identified by ¹H-NMR, ¹³C-NMR (APT), and elemental analysis data. These hybrid compounds represent a promising class of anticancer agents. Several compounds demonstrated marked and concentration-dependent cytotoxicity across all cancer cell lines, with HeLa cells showing the highest overall sensitivity. The introduction of an oxadiazole ring (compound 7) and coumarin substituents (compounds 12b–12d) markedly improved anticancer activity and selectivity, yielding low-micromolar IC₅₀ values in HeLa cells (10.6–13.6 µM) and high Selectivity Indexes (SI = 2.0–3.63). Compound 6 also exhibited balanced potency across A549, MCF-7, and HeLa cells (IC₅₀ = 28.3–31.2 µM) with SI values ≥ 2.0. Compound 9 showed strong cytotoxicity across all cancer cell lines; its moderate SI values indicate lower discrimination between malignant and non-malignant cells. Taken together, these findings identified compounds 7, 12b–12d, 6, and 12c as the most promising benzimidazolone-based candidates, displaying both potent cytotoxicity and favorable selectivity over non-malignant HEK293 cells. Conclusions: Among the synthesized molecules, the oxadiazole derivative (7) and the coumarin-based hybrids (12b–12d) exhibited the strongest combination of cytotoxic activity and selectivity, reflected by their low IC₅₀ values and high SI ratios. Notably, compound 12c combined strong biological activity with the highest predicted VEGFR2 affinity in the series, highlighting it as a particularly promising scaffold. While compound 9 exhibited excellent docking scores toward both VEGFR2 and CDK4, its lower selectivity suggests a need for further structural refinement. Overall, the biological and computational findings converge to identify these benzimidazolone hybrids as credible lead candidates for future anticancer optimization. Full article

It remains unclear how metabolites produced by vaginal peroxide-producing lactobacilli influence parameters supporting cervical cancer cell survival. The aim of our study was to investigate the functional response of HeLa cells to cell-free metabolites of vaginal lactobacilli producing peroxide under conditions of oxidative stress. HeLa cells were treated with cell-free metabolites of lactobacilli isolated from the vaginal fluid of healthy women. Subsequently, their resistance to oxidative stress (total number of surviving, apoptotic, and necrotic cells), dehydrogenase activity with the MTT assay, and mitochondrial potential were measured. Pretreatment with cell-free lactobacilli metabolites significantly reduced HeLa cell survival under oxidative stress in most cases; dehydrogenase activity and mitochondrial potential changed to a lesser extent. All HeLa cells pretreated with cell-free lactobacillus metabolites that died due to oxidative stress died apoptotic death. These effects of cell-free lactobacilli metabolites are not always determined by lactic acid levels. These data reveal a new mechanism by which vaginal lactobacilli exert local antitumor protection by inducing controlled cell death in transformed cells. Full article

The development of antibiotic resistance has become a global health challenge, resulting in approximately 800,000 deaths per year. The rapid rise in multidrug-resistant (MDR) pathogens has prompted an urgent need for antimicrobial alternatives. Punica granatum L. peel has long been valued for its rich bioactive polyphenols with potent antimicrobial properties. In this study, P. granatum L. peel extract (PGPE) was integrated with chitosan nanoparticles (CH-PGPE) to enhance antimicrobial efficacy while minimizing potential cytotoxicity. The antimicrobial potential of PGPE and CH-PGPE was evaluated with agar well diffusion, disk diffusion, and minimum inhibitory concentration (MIC) analyses against standard ATCC and clinical MDR strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. MTT assay evaluated the biocompatibility and anti-proliferative potential of PGPE on ARPE-19 (normal retinal pigment epithelial), HeLa (human cervical cancer), and A549 (human lung carcinoma) cell lines. PGPE exhibited antibacterial activity, and CH-PGPE reduced MIC values by approximately two-fold. Both PGPE and CH-PGPE demonstrated comparable or superior inhibition compared to several conventional antibiotics, particularly against MDR strains. The MTT assay revealed that PGPE was non-cytotoxic to normal ARPE-19 cells, while exhibiting the highest antiproliferative potency against A549 cells and a moderate inhibitory response in HeLa cells. The nanoparticle-supported formulation enhanced the antimicrobial efficacy of PGPE and also exhibited selective anti-proliferative activity against cancer cells without affecting normal cells. Full article

While tropical regions have traditionally been the focus of studies on natural bioactive products, works published within the last decade demonstrate that cyanobacteria from the Baltic Sea also possess significant biotechnological and pharmaceutical potential. The Baltic Pseudanabaena galeata CCNP1313 previously demonstrated activity against breast cancer cell lines (MCF7 and T47D) and several viruses. In the present study, the cytotoxicity of cellular extract and flash chromatography fractions from the strain were evaluated against a wider panel of cancer cells (A549, C-33A, CaSki, DoTC2, HeLa, PC3, SiHa, and T47D). To gain better insight into the compounds potentially responsible for the observed effects, high-resolution mass spectrometry was combined with bioactivity-based molecular networking. Both the extract and hydrophobic fractions showed strong cytotoxicity, particularly against breast cancer cells and selected cervical cancer cells. While HRMS analyses confirmed the production of previously characterised peptides by CCNP1313 (Pseudanabaena galeata peptides and galeapeptins), neither of them was found to be responsible for the activity. Instead, the molecular networking approach linked the cytotoxicity to specific lipid classes, including diacylglycerols (DAGs) and monogalactosyldiacylglycerols (MGDGs). This study highlights the necessity of integrating traditional methods with advanced bioinformatics for the successful discovery of bioactive natural products, especially when complex samples, such as extract or chromatographically separated fractions, are analysed. Full article