Cervical Cancer Cell Line HeLa Research Articles

Chrysotoxine regulates ferroptosis and the PI3K/AKT/mTOR pathway to prevent cervical cancer

Ethnopharmacological relevanceDendrobium (commonly known as Shihu in China), a traditional Chinese medicinal herb recognized in the Pharmacopoeia of China (2020 edition), boasts a rich history of medicinal application. Extensive research has been conducted on its Chinese medicinal prescription due to its demonstrated anti-tumour effects in clinical settings. Dendrobium is comprised of a diverse range of chemical compounds, notably the Bibenzyls, Erianin, and Gigantol, which have exhibited significant inhibitory and therapeutic effects on cervical cancer, thereby suggesting potential therapeutic value. However, the comprehensive investigation of Chrysotoxine, a naturally occurring active ingredient of Bibenzyls in Dendrobium, remains incomplete in treatment of cervical cancer. Aims of the studyThis study aimed to conduct a comprehensive investigation of Chrysotoxine and its regulatory impact on ferroptosis in cervical cancer. Materials and methodsInitially, the effects of chrysotoxine on the cervical cancer cell line HeLa were assessed using CCK-8, transwell, colony formation, and flow cytometry to evaluate cell proliferation, invasion, migration, and apoptosis. Subsequently, network pharmacology and molecular docking techniques were employed to identify the molecular targets of chrysotoxine in cervical cancer. Finally, confocal microscopy assessed the expression levels of ROS and lipid compounds in response to chrysotoxine treatment, and the influence of chrysotoxine on signaling pathways was investigated using Western blot analysis, guided by KEGG pathway analysis. ResultsOur cell-based experiments revealed that CTX effectively suppresses the cell proliferation, migration, invasion, and apoptosis in CC. Subsequently, we comprehensively analyzed that HSP90AA1, ESR1, PIK3CA, mTOR and MAPK1 may be the possible targets of CTX in CC by combining network pharmacology with molecular docking techniques. Finally, we observed that CTX enhances the production of intracellular ROS and excessive lipid peroxides. Simultaneously, we detected that CTX promotes ferroptosis-based p53/GPX4/SLC7A11 pathway and inhibits PI3K/AKT/mTOR pathway-induced cell death of CC by Western blot. ConclusionOur study indicates that chrysotoxine shows promise as a novel medication for treating CC. The findings provide a scientific foundation for the regulation of cervical cancer by chrysotoxine, presenting new insights into the application of traditional Chinese medicine for fighting CC.

Citric acid functionalized neomycin carbon dots for cytotoxicity and sensing application

Carbon nanomaterials have been applied in various fields. Currently, functionalized carbon nanomaterial with practical tuning and surface functionalization is a tremendously used method. Herein, neomycin-based fluorescent carbon quantum dots were synthesized via hydrothermal method using neomycin and citric acid as a source for selective sensing of Fe3+ metal ions. The as-prepared Neo-CA-CQDs exhibited blue fluorescence, successfully characterized and utilized for sensing various metal ions. The carbon dots showed excellent sensing properties towards Fe3+ metal ions and optical properties were characterized by a fluorescence spectrofluorometer. In addition, pH and biocompatibility studies were investigated for the Neo-CA-CQDs. The average size of the Neo-CA-CQDs was 3–5.7 nm. The quantum yield of the as-prepared Neo-CA-CQDs was 29.3 %. The limit of detection for Fe3+ sensing was determined to be 6.09 μM. The sensing of Fe3+ ions was also confirmed through visual detection, as a significant color change of the CQDs was observed. Additionally, a competitive study was conducted to verify the selectivity of the neomycin citric acid-mediated CQDs towards Fe3+. The in vitro cytotoxicity study was performed on a mouse fibroblast cell line (L929) and Human cervical cancer cell line (HeLa).

Synthesis, crystal structure, cytotoxicity (MCF-7 and HeLa) and free radical scavenging activity of the hydrazones derived from 2-methylsulfonyl-5-nitrobenzaldehyde

The rising levels of breast and cervical cancers among women have become public health problem with high economic burden globally and more especially in low- and middle-income countries. This necessitates discoving new and potent anticancer drugs with reduced or no side effects. The hydrazones derived from 2-formyl-4-nitrophenyl methanesulfonate were characterized using a combination of spectroscopic and single-crystal X-ray diffraction (XRD) techniques. The compounds were, in turn, evaluated for antigrowth effect in vitro against the human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The presence of a chlorine atom on the para position of the phenylhydrazone moiety of 3b resulted in increased cytotoxicity against the MCF-7 and the HeLa cell lines compared to camptothecin (IC50 = 9.15 ± 0.84 µM and 3.71 ± 0.16 µM, respectively) with IC50 values of 5.64 ± 0.84 µM and 2.40 ± 0.13 µM, respectively. Compounds 2, 3a and 3b were found to exhibit significantly reduced toxicity against the Vero cells compared to the anti-cancer drugs, doxorubicin (IC50 = 0.78 ± 0.04 µM) and nintedanib (IC50 = 0.24 ± 0.02 µM) with the IC50 values of 17.86 ± 1.12, 11.89 ± 1.01 and 24.42 ± 0.70 µM, respectively. The hydrazones 3a and 3b exhibited a strong inhibitory effect against the vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase (IC50 = 5.78 ± 0.039 μM and 5.79 ± 0.053 µM, respectively) compared to the carbaldehyde precursor 2 (IC50 = 8.01 ± 0.052 µM) though less active compared to nintedanib (IC50 = 1.05 ± 0.193 µM). The hydrazone derivatives exhibited significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity compared to ascorbic acid and the parent 2-formyl-4-nitrophenylmethanesulfonate. In silico molecular docking studies revealed the binding potential of the hydrazones at the active site of VEGFR-2 tyrosine kinase and cytochrome c peroxidase.

Chemical Profile of Kumquat (Citrus japonica var. margarita) Essential Oil, In Vitro Digestion, and Biological Activity.

Kumquat is one of the smallest citrus fruits (from the Rutaceae family), and its essential oil's biological effects have not yet been sufficiently researched, in contrast to the essential oils of its relatives. Therefore, the aim of this large-scale study was to investigate the chemical profile of kumquat essential oils (KEOs) isolated by microwave-assisted distillation (MAD) and Clevenger hydrodistillation using GC-MS analysis. To test the bioaccessibility of their bioactive components, in vitro digestion with commercially available enzymes was performed. The final step of this research was to test their cytotoxic activity against a cervical cancer cell line (HeLa), a human colon cancer cell line (HCT116), a human osteosarcoma cell line (U2OS), and a healthy cell line (RPE1). Two methods were used to test the antioxidant activity: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). The antibacterial activity was tested in relation to the growth and adhesion of Escherichia coli and Staphylococcus aureus on a polystyrene surface. The GC-MS analysis showed that the major compound in both kumquat essential oils was limonene, which was stable before and after in vitro digestion (>90%). The results showed that the cytotoxic activity of the KEOs in all three cancer cell lines tested was IC50 1-2 mg/mL, and in the healthy cell line (RPE1), the IC50 value was above 4 mg/mL. The antibacterial activity of the KEOs obtained after MAD and Clevenger hydrodistillation was 4 mg/mL against E. coli and 1 mg/mL against S. aureus. The KEOs after MAD and Clevenger hydrodistillation reduced the adhesion of E. coli by more than 1 log, while there was no statistically significant effect on the adhesion of S. aureus to the polystyrene surface. Both KEOs exhibited comparable levels of antioxidant activity using both methods tested, with IC50 values of 855.25 ± 26.02 μg/mL (after MAD) and 929.41 ± 101.57 μg/mL (after Clevenger hydrodistillation) for DPPH activity and 4839.09 ± 91.99 μmol TE/g of EO (after MAD) and 4928.78 ± 275.67 μmol TE/g of EO (after Clevenger hydrodistillation) for ORAC. The results obtained show possible future applications in various fields (e.g., in the food, pharmaceutical, cosmetic, and agricultural industries).

Gamma irradiation green synthesis of (polyacrylamide/chitosan/silver nanoparticles) hydrogel nanocomposites and their using as antifungal against Candida albicans and anti-cancer modulator

Silver nanoparticles-loaded hydrogel nanocomposites are exploited for medicinal and pharmaceutical applications. Hydrogel nanocomposites were prepared from acrylamide (Am), chitosan (CS) and AgNO3 utilizing gamma rays. Diverse variables were applied in preparation of silver nanoparticles-laoded hydrogel nanocomposites of (PAm/CS)-AgNPs such as influence of radiation dose and influnece of CS concentration. Diverse techniques were utilized to characterize hydrogel nanocomposites; Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), Transmission electron microscopy (TEM), energy dispersive X-ray (EDX) and scanning electron microscopy (SEM). Results confirmed formation of silver nanoparticles-loaded hydrogel nanocomposites of (PAm/CS)-AgNPs. Antifungal activity of (PAm/CS)-AgNPs hydrogel nanocomposites on viability of C. albicans was esitmated. Results displayed the efficient microbial inhibition activity of treatment against C. albicans compared to control. Furthermore, (PAm/CS)-AgNPs hydrogel nanocomposite against cervical cancer HeLa cell line was investigated. Cytotoxicity of (PAm/CS)-AgNPs hydrogel nanocomposites on prior cancer cell line empolyed to prohibition of cell growth assesssed by MTT test. HeLa cancer cell is treated by (PAm/CS)-AgNPs for 48 h exposed a potential apoptotic activity by noticeable up-regulation of p53 gene expression. Moreover, anticancer activity was investigated by down-regulation of platelet-based growth variable receptor beta (PDGFR-β), Bcl2, Cathepsine, and MMP-2 gene expression. antioxidant activity was investigated and results showed antioxidant activity of (PAm/CS) hydrogel and (PAm/CS)-AgNPs hydrogel nanocomposite are 87.8% and 62.9%, respectively.

Unveiling the anticancer potential: Exploring 4-fluoro benzoic acid and piperazine through spectroscopic, X-ray diffraction, DFT and molecular docking analysis

The crystalline substance formed from piperazine and 4-fluorobenzoic acid (PZ-PFBA) was successfully synthesized. This synthesis involved the transfer of protons between the selected acid and base, resulting in the formation of distinct crystalline salt. The SCXRD analysis conforms the salt crystallized in a monoclinic crystal system with a P 21/c space group and lattice parameters are a = 13.0688(14) Å, b = 8.2686(8) Å, and c = 8.2552(9) Å. Hirshfeld surface analysis, a technique for quantifying molecular interactions, was employed to investigate the prepared crystalline salt. Additionally, the salt was subjected to further examination using FT-IR, 1H NMR, 13C NMR, and SCXRD studies. The crystalline salt has major and established biological actions that inhibit the human lung cancer cell line A549. In vitro, and Insilico anticancer tests show that PZ-PFBA has better efficacy against the human cervical cancer cell line (HeLa) and in bioinformatics analysis. PZ-PFBA demonstrated more efficacy in reducing pathogenic strains compared to its parent reactants.

BODIPY photosensitizers functionalized with mannose for fluorescence cell-imaging and photodynamic therapy

The synthesis of four water-soluble mannose-tethering BODIPY-based photosensitizers (PSs) with varying substituents (H, OMe, NO2 and I) in the para-phenyl moiety attached to the meso-position of the BODIPY core, offering tumor-targeting and photodynamic therapeutic (PDT) potentials, is reported. The PDT capability of the synthesized PSs was investigated using the cervical cancer cell line HeLa. Owing to the heavy atom effect, BODIPY I, enhanced the intersystem crossing (ISC) to produce singlet oxygen (1O2) and maintained a high fluorescence quantum yield (ΦF) of 0.71. In contrast, the electron-donating methoxy substituent (BODIPY OMe) caused a notable perturbation in the occupied frontier molecular orbitals, subsequently achieving a higher 1O2 generation capability with a high ΦF of 0.85. Conversely, substitution with the electron-withdrawing nitro group (BODIPY NO2) resulted in a perturbation of unoccupied frontier molecular orbitals and generated a forbidden dark S1 state, negatively affecting both fluorescence and 1O2 generation efficiencies. The cytotoxicity of the synthesized water-soluble BODIPY PSs in the dark and under LED irradiation against the HeLa cell line was also assessed, with BODIPY I, OMe and H showing favorable PDT activity. Collectively, the performance of the mannose-conjugated BODIPY PSs in this study contributed promising results for the development of photodynamic therapeutic agents for cancer treatment.

The Effect of Quercetin on the Expression of miR-21 and miR-34a-5p on HeLa and Ca Ski Cell Lines

Background: Cervical cancer is the fourth most common cancer among women. In recent years, significant progress has been made in its treatment. Quercetin, a polyphenolic compound found in flavonoid-containing plants, is of interest due to its potential therapeutic effects. miR-21 plays a crucial role in cervical tumor metastasis by activating pathways related to invasion and migration, while miR-34a-5p is essential in regulating epithelial-to-mesenchymal transition and preventing increased cell proliferation and migration. The findings of this study could provide insight into the role of quercetin in cancer cells. Objectives: This study aims to investigate the effect of quercetin on the expression levels of miR-21 and miR-34a-5p in HeLa and Ca Ski cervical cancer cell lines. Methods: In this study, HeLa and Ca Ski cells were treated with quercetin. Cell viability and apoptosis were evaluated using the MTT assay and flow cytometry over a 48-hour period. Additionally, the effects of quercetin on the expression levels of miR-21 and miR-34a-5p were analyzed using qRT-PCR. Results: The study demonstrated that quercetin inhibited the viability of HeLa and Ca Ski cells and induced apoptosis in these cells. Quercetin suppressed cell viability with an IC50 of 102.9 μM for HeLa and 304.1 μM for Ca Ski cells after 48 hours. Quercetin down-regulated miR-21 in HeLa and Ca Ski cell lines by 2.5 ± 0.1 (P = 0.045) and 2.0 ± 0.2 (P = 0.016) fold, respectively. Additionally, miR-34a-5p increased by 3.3 ± 0.7 (P = 0.010) and 2.4 ± 0.8 (P = 0.047) fold after exposure to quercetin in HeLa and Ca Ski cell lines, respectively. Conclusions: Our study showed that quercetin has an anti-cervical cancer effect and can be used alongside standard therapies as a promising agent with fewer side effects in cervical cancer treatment.

Green Synthesis of Dracocephalum kotschyi-Coated Silver Nanoparticles: Antimicrobial, Antioxidant, and Anticancer Potentials.

BACKGROUND The environmentally friendly production of silver nanoparticles (AgNPs) has gained significant attention as a sustainable alternative to traditional chemical methods. This study focused on synthesizing AgNPs using extract of Dracocephalum kotschyi (D. kotschyi), a medicinal plant. MATERIAL AND METHODS The biosynthesis of AgNPs was monitored using UV-visible spectrophotometry. The role of phytoconstituents from D. kotschyi in stabilizing AgNPs was analyzed using Fourier-transform infrared (FTIR) spectroscopy. Dynamic light scattering (DLS) spectroscopy was used to determine the size, charge, and polydispersity of the nanoparticles, while scanning electron microscopy (SEM) was employed to assess their morphology. We evaluated the antimicrobial efficacy of the synthesized AgNPs against various bacteria, their antioxidant properties via a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, and their cytotoxic activity against the HeLa cervical cancer cell line. RESULTS The formation of AgNPs was indicated by a color change and the emergence of a surface plasmon resonance peak at 418 nm. The nanoparticles demonstrated significant antimicrobial, antioxidant, cytotoxic, and anticancer activities. Morphology, size, and shape analysis revealed nearly spherical particles with an average size of 43 nm. FTIR confirmed the presence of phenolic compounds in the extract, serving as reducing and capping agents. X-ray diffraction (XRD) analysis confirmed the crystalline structure of the nanoparticles. Antimicrobial assessments showed effectiveness against Escherichia coli and Staphylococcus aureus. The DPPH scavenging assay demonstrated efficient antioxidant activity, and potent apoptotic anticancer effects were observed on cervical cancer cells. CONCLUSIONS The extract of D. kotschyi was effective as a reducing agent in the environmentally friendly synthesis of AgNPs, which exhibited noteworthy antimicrobial, antioxidant, and anticancer properties. These findings suggest potential biomedical applications for the synthesized AgNPs.

Multifaceted insights into Cu(II) complexes with bis(benzimidazole) ligands: Structural investigation, theoretical studies, cytotoxicity evaluation, and antioxidant summarizing

In this study, the synthesized two new ligands, namely bis(1H-benzo[d]imidazole-1-yl) methane [L1] and 1,2-bis(1H-benzo[d]imidazole-1-yl) ethane [L2], from benzimidazole. They chose 1,2-dibromomethane and 1,2-dibromoethane as they are widely used in environmental catalysis and as ligands in conjugated configurations. The researchers were able to synthesize the Cu(II) complexes, [Cu(L1)2]Cl2 or [1] and [Cu(L2)2]Cl2 or [2], at room temperature. They used several analytical techniques, including elemental analysis, magnetic moment measurement, UV–visible spectroscopy, FT-IR spectroscopy, FT-Raman spectroscopy, NMR spectroscopy (including 1H, 13C, DEPT-135, HSQC, and HMBC techniques), ESI-MS analysis, thermogravimetric analysis, and ESR spectroscopy, to characterize the synthesized compounds. They found that the ESR spectra of complexes [1] and [2] suggest that both metal complexes have square planar coordination spheres. In the DFT study of the geometrical optimization of both complexes, the central plane consists of the Cu metal atom connected to four nitrogen atoms. The Cu–N bond lengths are measured at 2.194 Å for [1] and 2.176 Å for [2] whereas the FMO theory's slight reduction in the HOMO-LUMO gap for [2] suggests that it is more reactive and less stable compared to [1]. In addition, the researchers tested the effect of these compounds on human cervical cancer cell lines (HeLa) which showed significant cytotoxic effects under laboratory conditions. Complex [2] had a significant inhibitory impact on the growth of cancer cells. The researchers also assessed the antioxidant effects of the ligands and metal complexes using DPPH, OH, and NO assays and found that [2] had the most potent inhibitory effect on the radicals, with IC50 values of 36.11 μM (DPPH), 28.18 μM (OH), and 26.20 μM (NO).

Preparation and Evaluation of Polyethylene Glycol Conjugated Polyethylene Imine‐Coated Magnetic Nanoparticles for Paclitaxel Delivery to Cervical Cancer Cells

ABSTRACTThe purpose of this study was to synthesize and characterize the therapeutic effect of paclitaxel‐loaded polyethylene glycol modified polyethylene imine‐coated iron oxide nanoparticles on cervical cancer cell line (HeLa cell). The physiochemical characteristics of nanocarriers were confirmed by using several methods including X‐ray diffraction (XRD), Thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT‐IR), Vibrating sample magnetometer (VSM), Dynamic light scattering (DLS), and Transmission electron microscopy (TEM). The results showed the magnetic nanoparticles with size of 35 nm and excellent magnetic properties could load paclitaxel with capacity (16%) and encapsulation efficiency (80%) that has revealed pH‐dependent release behavior. The anticancer effects of nanoparticles were investigated using MTT assay. In comparison to free drug, paclitaxel‐loaded magnetic nanocarrier revealed more cytotoxicity against HeLa cell line and also resulted in an increased rate of apoptotic cancer cells, assessed by flow cytometry analysis. Furthermore, the developed magnetic nanocarrier showed suitable hemocompatibility which can be used in clinical applications.

Determination of Cytotoxic Activity of Aronia melanocarpa (Michx.) Elliot Fruit Extracts on Breast Cancer (MCF-7) and Cervical Cancer (HeLa) Cell Lines

Aronia (chokeberry) fruits are consumed as fresh fruit due to their high antioxidant activity, and are also preferred among the public in the production of natural medicines. Aronia melanocarpa (Michx.) Elliot, a species of the Rosaceae family, contains many phytochemical compounds such as flavonoids, phenolic compounds, lignans, terpenes, tocopherols, phospholipids, organic acids and high amounts of anthocyanins. In this study, it was aimed to determine the in vitro anticarcinogenic activities of A. melanocarpa (Michx.) Elliot fruit extracts prepared with 6 different solvents. In the study, the cytotoxic effects of the fruits were investigated using breast cancer cell line (MCF-7) and cervical cancer cell line (HeLa), and their effects on healthy cells were investigated using human endothelial cells (HUVEC) and mouse fibroblast cells (L929) by the MTT method. As a result of the study; It was determined that the highest cytotoxicity on the breast cancer (MCF-7) cell line was observed in the ethanol extract (IC50=111.44 µg/mL) and the lowest cytotoxicity was observed in the hexane extract (IC50=661.80 µg/mL). It was determined that the highest cytotoxicity on the cervical cancer (HeLa) cell line was observed in the ethanol extract (IC50=95.14 µg/mL) and the lowest cytotoxicity was observed in the ethyl acetate extract (IC50=319.51 µg/mL). According to these values; It was determined that all extracts of Aronia fruit had cytotoxic effects on MCF-7 and HeLa cell lines, selectivity index values were higher in HeLa cells, and they did not have cytotoxic effects on HUVEC and L929 healthy cell lines (IC50=411.25-663.27 µg/mL). Thus, it has been determined that the fruits of the Aronia melanocarpa species are promising in the development of new natural resources, new drugs and therapeutic agents in cancer treatment, thanks to their anticancer activities and low cytotoxicity. It is recommended that further research be conducted on the mechanisms of anticancer activity in the future

Phytochemical Profiling of Aquilaria malaccensis Lam. Essential Oils and their Antiproliferative Potential against HeLa Human Cervical Cancer Cells

Background: Aquilaria malaccensis Lam. is one of the very few lign-aloes trees that can produce highly valuable resin-impregnated heartwood, commonly known as agarwood. Aim: This study aimed to determine the chemical profile of A. malaccensis essential oil and describe its antiproliferative effects against the HeLa cervical cancer cell line for the first time. Method: The essential oils hydro-distilled from agarwood were characterised using GC−MS with the aid of spectral deconvolution. The antiproliferative effects were evaluated via the MTT assay. Result: A total of 143 metabolites were tentatively identified in two different grades of essential oils, which accounted for 56.80% and 78.19% of the total ion counts, respectively. These metabolites were distributed over the chemical families of monoterpenes, sesquiterpenes, cyclic hydrocarbons, and others. The essential oils exhibited antiproliferative activities, with IC50 values of 79.42 and 128.77 μg/mL, respectively. Conclusion: The results have suggested the chemical differences in secondary compounds to be the main factor contributing to the decrease in cell viability. Further investigations are warranted to understand its mechanisms of action and its potential use in cervical cancer treatment.

Bioactive secondary metabolites from an endophytic fungus Aspergillus sp. CCH-1E from Catharanthus roseus

This study focused on the bioactive secondary metabolites of an endophytic fungus Aspergillus sp. CCH-1E from Catharanthus roseus. The secondary metabolites from Aspergillus sp. CCH-1E were isolated by using various chromatographic methods [such as normal-phase and reversed-phase chromatography and high-performance liquid chromatography(HPLC)], and their structures were identified by various spectroscopic methods [e.g., ultraviolet(UV) spectroscopy, infrared(IR) spectroscopy, nuclear magnetic resonance(NMR) spectroscopy, and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS)]. Twelve compounds were yielded and identified from Aspergillus sp. CCH-1E, which are chermesinone H(1), chermesinone I(2), chermesinone B(3), 8,11-didehydrochermesinone B(4), chermesinone C(5), chermesinone A(6), chevalone B(7), barbacenic acid(8), 3,6,8-trihydroxy-3,5,7-trimethyl-3,4-dihydroisocoumarin(9), 5-hydroxy-2-methoxy-7-methyl-1,4-naphthoquinone(10), 1-hydroxy-6,8-dimethoxy-3-methylanthracene-9,10-dione(11), and 7-drimen-9α,11,12-triol(12). Among them, compounds 1 and 2 are new compounds. The growth inhibition effects of all compounds were evaluated against non-small cell lung cancer cell lines A549 and NCI-H1650, as well as human cervical cancer cell line HeLa by using methylthiazolyldiphenyl-tetrazolium bromide(MTT). Compound 7 significantly inhibited the growth of three tumor cells with the IC_(50) values of 1.22-2.43 μmol·L~(-1), respectively. Compounds 1-6 showed moderate cell growth inhibition with the IC_(50) values of 16.24-35.28 μmol·L~(-1).

Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line.

This study aimed to assess linagliptin's inhibitory effects on the proliferation of cervical cancer cell lines and investigate its potential for targeting human heat shock protein 90. Linagliptin's cytotoxicity was assessed on a cervical cancer cell line (Hela cancer cell line) at two different incubation periods, 24 and 72 hours. The molecular docking between linagliptin and the receptor protein human Hsp 90 (PDB code: 5XRE) was performed using the Biovia Discovery Studio and AutoDock tool software. The Discovery Studio visualizer generated three-dimensional (3D) and two-dimensional (2D) interactive images. The study's cytotoxicity results demonstrated that linagliptin can inhibit the proliferation of cervical cancer cells. The cytotoxicity exhibited a time-dependent pattern (cell cycle specific). The molecular docking study was conducted to investigate the interaction between linagliptin and human Hsp90. The study identified 11 sites where linagliptin can bind to Hsp90 amino acid residues. The total docking score for this interaction was -10.3 kcal/mol. The most potent binding occurred through conventional hydrogen bonds with the ASP:54 amino acid residues at a distance of 2.93 Å. The docking scores for linagliptin were comparable to those of the reference drug geldanamycin, indicating a strong interaction between linagliptin and Hsp90. The study has found that linagliptin successfully reduces the growth of cervical cancer cells with a time-dependent cytotoxic pattern. The potential anticancer mechanism of linagliptin can be inferred by analyzing the docking score and docking pattern between linagliptin and Hsp90, suggesting that linagliptin targets human Hsp 90.

Triptolide-induced cuproptosis is a novel antitumor strategy for the treatment of cervical cancer

BackgroundCuproptosis is a unique copper-dependent form of cell death that is highly correlated with the metabolic state of cells. Triptolide exerts pharmacological activity by altering the regulation of metal ions. Cuproptosis is poorly understood in cancer, so in this study, we explored whether triptolide could induce cuproptosis in cervical cancer cells.MethodsThe human cervical cancer cell lines HeLa and SiHa, which primarily rely on oxidative phosphorylation, were treated with triptolide. Cell viability, proliferation and migration, copper levels and cuproptosis-related protein levels were evaluated in these cell lines. The copper ion chelator tetrathiomolybdate (TTM) was administered to determine whether it could reverse the cuproptosis induced by triptolide. In addition, a nude mouse cervical cancer xenograft model was established to determine the effects of triptolide on cuproptosis in isolated tumor tissues.ResultsThe copper concentration increased with triptolide treatment. The levels of cuproptosis -related proteins, such as FDX1, LIAS, and DLAT, in the HeLa and SiHa cell lines decreased with triptolide treatment. XIAP, the target of triptolide, played a role in cuproptosis by regulating COMMD1. The level of copper exporters (ATP7A/B) decreased, but the level of the copper importer (CTR1) did not change with triptolide treatment. Furthermore, triptolide inhibited cervical cancer growth and induced cuproptosis in vivo.ConclusionsIn summary, we report a new antitumor mechanism by which triptolide disrupted intracellular copper homeostasis and induced cuproptosis in cervical cancer by regulating the XIAP/COMMD1/ATP7A/B axis.

Royal Jelly–Mediated Silver Nanoparticles Show Promising Anticancer Effect on HeLa and A549 Cells Through Modulation of the VEGFa/PI3K/Akt/MMP‐2 Pathway

ABSTRACTIn recent years, nanotechnology has revolutionized various sectors, particularly in nanomedicine, where nanomaterials are used for diagnosis, monitoring, control, prevention, and treatment. Among these, silver nanoparticles (AgNPs) stand out due to their remarkable antimicrobial and cytotoxic properties. Traditional chemical synthesis of AgNPs poses significant environmental and health risks. This study introduces a novel, eco‐friendly synthesis method using royal jelly (RJ), a nutrient‐rich secretion from honeybees, to produce AgNPs with potent anticancer effects. Our research provides a detailed investigation into RJ‐mediated AgNPs’ modulation of the VEGFa/PI3K/Akt/MMP‐2 pathway in HeLa and A549 cancer cell lines. AgNP characterization was performed by applying UV–Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) in combination with selected area electron diffraction (SAED). Cell signaling system components were determined by ELISA analysis. The cells were subjected to staining with hematoxylin and eosin to visualize the treatment’s effects. This study focuses on the green synthesis of AgNPs using RJ and its bioactivity against cancer cells. It provides a detailed characterization of the nanoparticles and examines their effects on cancer cells, specifically HeLa cervical cancer and A549 lung cancer cell lines. Green synthesized AgNPs demonstrate significant cytotoxic effects against HeLa and A549 cancer cell lines. The underlying molecular mechanisms contributing to their anticancer activity were elucidated. Our findings revealed a significant decrease in arginase activity upon exposure to AgNPs, accompanied by reductions in PI3K and phosphorylated and total Akt levels, indicative of pathway inhibition. Additionally, RJAgNP demonstrated a capacity to reduce nitric oxide levels and suppress angiogenesis‐related factors like VEGF and MMP‐2 and inflammation‐related factors like TNF‐α and COX‐2, thus impeding angiogenesis and metastasis. Moreover, our results shed light on the involvement of reactive oxygen intermediates (ROIs) in mediating apoptotic pathways, as evidenced by the increase in malondialdehyde (MDA) concentration and the corresponding decrease in Akt levels, ultimately promoting death in cancer cells. Our study contributes significantly to the field of nanomedicine and cancer therapy by introducing the use of green synthesis AgNPs using RJ and providing in‐depth insights into their molecular mechanisms of anticancer action. Our research findings demonstrate the anticancer potential of RJ‐AgNPs by targeting the VEGFa/PI3K/Akt/MMP‐2 pathway and modulation of ROS/RNS in cancer cells.

GC–MS analysis, molecular docking, and apoptotic-based cytotoxic effect of Caladium lindenii Madison extracts toward the HeLa cervical cancer cell line

Utilizing medicinal plants and other natural resources to prevent different types of human cancers is the prime focus of attention. Cervical cancer in women ranks as the fourth most common type of malignancy. The current study used gas chromatography-mass spectrometry (GC–MS) to identify the active phytochemical constituents from Caladium lindenii leaf extracts using ethanol (ECL) and n-hexane (HCL) solvents. Plant extracts were tested for potential cytotoxic effects on HeLa and HEK-293 T cells using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and the crystal violet assays. SYBR Green-based real-time PCR was performed to assess the mRNA expression profile of the apoptosis biomarkers (BCL-2 and TP53). The molecular interaction of the compounds with the targeted proteins (TP53, BCL2, EGFR, and HER2) was determined using molecular docking. GC–MS analysis revealed a total of 93 compounds in both extracts. The ECL extract significantly reduced the proliferation of HeLa cervical cancer cells, with an IC50 value of 40 µg/mL, while HEK-293 T cells showed less effect (IC50 = 226 µg/mL). The quantitative RT-PCR gene expression analysis demonstrated the ethanol extract regulated TP53 and BCL2 mRNA expressions in treated cancer cell samples. Heptanediamide, N,Nʹ-di-benzoyloxy-(− 10.1) is the best-docked ligand with a TP53 target found in the molecular docking study, whereas EGFR/Clionasterol had the second highest binding affinity (− 9.7), followed by EGFR/Cycloeucalenol (− 9.6). It is concluded that ECL extract has promising anti-cervical cancer potential and might be valued for developing new plant-derived anticancer agents after further investigations.

In vitro cancer cell line luminescence-based validation of anticancer phytocompounds obtained from Leucas biflora against HELA cervical and A549 lung cancer cells.

Current research aims to screen the anticancer prospective of Leucas biflora phytocompounds against apoptotic regulator target protein essential for cancer progression. In gas chromatography-mass spectrometry analysis major phytocompounds such as tetracosahexaene, squalene, phytol, 22-stigmasten-3-one, stigmasterol, fluorene, and 1,4-dihydro were identified in ethanolic leaf extract of Leucas biflora. In vitro, the free radical scavenging potential of ethanolic leaf extract of Leucas biflora was examined through its DPPH and ABTS radical scavenging potential IC50 value 15.35 and 13.20 μg/ml, respectively. Dose-dependent cytotoxicity was monitored against both A549 lung cancer and HELA cervical cancer cells. Leucas biflora ethanolic leaf extract highly reduces the cell viability of both HELA and A549 cells in in vitro cytotoxicity assays. Leucas biflora ethanolic extract produces 23.76% and 29.76% viability rates against A549 lung and HELA cervical cancer cell lines, and their IC50 values differ slightly at 95.80 and 90.40 μg/ml, respectively. In molecular docking analysis lung cancer target protein-ligand complex 5Y9T-16132746 showed a maximum score of -14 kcal/mol by exhibiting stable binding affinity and interactions among all screened complexes. Based on docking score nine phytocompounds from Leucas biflora and two reference standard drugs were chosen for further analysis. Further validation reveals that the fluorene, 1,4-dihydro possess good ADMET, Bioactivity and density functional theory indices.

Inhibitory effect of Curcumin on a cervical cancer cell line via the RAS/RAF signaling pathway.

Cervical cancer has a very important place in female infertility and ranks fourth among cancers affecting women. Curcumin (CUR) is closely associated with the expression and activity of various regulatory proteins. It is also known that curcumin has preventive and therapeutic effects on various types of cancer. In this study, the anticancer activities of curcumin were demonstrated in the human cervical cancer cell line (HeLa). qRT-PCR and western blot analyses were used to evaluate mRNA and protein expression of curcumin in HeLa and immortalized human skin keratinocyte cell lines (HaCaT) (proliferation and apoptosis regulatory markers of the RAS/RAF signaling pathway). MTT analysis was performed, showing HeLa and HaCaT cell proliferation depending on the dose and duration of curcumin and doxorubicin. A wound scratch healing assay was applied to examine cell migration and invasion of HeLa after curcumin application. To determine the role of curcumin and doxorubicin in the apoptosis of HeLa cells, the mRNA levels of caspase-3 were examined by qRT-PCR. The results were analyzed with a one-way ANOVA SPSS 20.0 program. CUR (IC50: 242.8 μM) and DOX (IC50: 92.1 μM) were determined to have the ability to inhibit the proliferation of HeLa cells and induce apoptosis over a 72-hour period and dose-dependently. Moreover, the results revealed that the mRNA and protein expression levels of RAF and RAS in HeLa cells were downregulated by CUR and DOX. The findings show that an alternative treatment method for cervical cancer can be developed with the application of CUR and DOX. Alternative methods for cervical cancer treatment may be developed using different methods in future studies.