Cervical Cancer Cell Line HeLa Research Articles

Evaluation of Cytotoxic, COX Inhibitory, and Antimicrobial Activities of Novel Isoxazole-carboxamide Derivatives

Abstract: Isoxazole derivatives are one of the heterocyclic structures that have various biological activities. Objective: This study aimed to design and synthesize novel isoxazole derivatives and evaluate their cytotoxic, cyclooxygenase (COX) inhibitory, and antimicrobial activities. Methods: Coupling reactions of aniline derivatives and isoxazole carboxylic acid have been established to synthesize chloro-fluorophenyl-isoxazole carboxamide derivatives. The synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and evaluated by MTS, COX kit, and antimicrobial microdilution assays. Results: The synthesized compounds showed moderate to potent cytotoxic activity against all the screened cancer cell lines (except 2b against HepG2) with an IC50 range of 0.107-77.83 μg/ml. The results showed that the most potent compound against cervical cancer cell line (HeLa) was the 2b compound, with an IC50 value of 0.11±0.10 μg/ml, which is less than the IC50 for the potent anticancer drug Doxorubicin. While the 2a and 2b compounds have potential antiproliferative activities against Hep3B with IC50 doses of 2.774±0.53 and 3.621±1.56 μg/ml, respectively. Furthermore, 2c compound was the most active against MCF7, with an IC50 value of 1.59±1.60 μg/ml. In addition, the most potent isoxazole derivative against the COX1 enzyme was the 2b compound, with an IC50 value of 0.391 μg/ml, and compound 2a had a good selectivity ratio of 1.44 compared to the Ketoprofen positive control. However, compound 2c showed antifungal activity against Candida albicans with an MIC value of 2.0 mg/ml in comparison to the antifungal drug Fluconazole (MIC = 1.65 mg/ml). Conclusion: The synthesized compounds could be candidates for anticancer drugs in the future, and other analogues and cytotoxicity evaluations should be conducted.

Synthesis and Biological Evaluation of 1-Substituted (R)-6-(2?-Cyano-1?-Pyrrolidin-yl)-4-(3?- Hydroxyadamantan-1?-yl)-3-phenyl-1,2,4-triazines

A series of various 1-substituted (R)-6-(2?-cyano-1?-pyrrolidin-yl)-4-(3?-hydroxy adamantan-1?-yl)-3-phenyl- 1,2,4-triazines (5a-i) was synthesized by the reaction of (R)-6-(2?-cyano-1?-pyrrolidin-yl)-4-(3?-hydroxy adamantan-1?- yl)-3-phenyl-1,4-dihydro-1,2,4-triazine (4) with heterocyclic halogenated compounds (R-X) in the presence of potassium carbonate. All the synthesized compounds were evaluated biologically and also determined In vitro cytotoxicity of compounds 5a, 5c, 5d, 5e, 5g, and 5h against human cervical cancer cell line (HeLa). Among all the synthesized compounds, some compounds exhibited potent antimicrobial activity as well as cytotoxicity.. KEYWORDS :1,2,4-Triazine, Adamantanol, Biological activities, Pyrrolidine.

Pllans-II: Unveiling the Action Mechanism of a Promising Chemotherapeutic Agent Targeting Cervical Cancer Cell Adhesion and Survival Pathways.

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient's quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans-II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans-II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α5β1 integrins and fibronectin of the extracellular matrix. Pllans-II reduces the cells' ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans-II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer.

Synthesis, Evaluation of anticancer and antimicrobial activities of some Schiff bases derivatives

In this research, compound [1,2-Bis-(4-amino-5-mercapto-4H-[1,2,4]triazol-3-yl)-ethane-1,2-diol] was used as starting material for synthesis different Schiff's Bases compounds. The fusion of tartaric acid with thiocarbohydrazide produce the compound (C1), the Schiff's bases (C2-C4) were created through the condensation of substances (C1) with different substituted benzaldehydes in presence of glacial acetic acid as catalyst. Thin layer chromatography (TLC) was used to confirm the compounds' purity, and spectroscopic methods were used to infer the compounds' structures (FTIR) and magnetic nuclear resonance spectroscopy (1H-NMR and 13C-NMR). The agar well diffusion method was used to test synthesized compounds for their antibacterial activity against K. pneumonia and S. aureus, and the findings were inconsistent. Target substances were tested for their ability to kill human breast cancer at concentrations of 50 and 100 g/mL. Human muscle tissue HC normal cell line, human cervical cancer Hela cell line, and HePG2 cell line. The results showed that the chemicals had potential cytotoxic activity against the Hela cell line, particularly compound (C4), which had the greatest inhibition at doses of 100 mg/mL among the examined substances

Smart perhydroxycucurbit [6] uril functionalized magnetic graphene oxide for release of Naringin as an antitumor agent

In this study, a mix ferrite (Zn0.6Co0.4Fe2O4) was immobilized on graphene oxide via a one pot hydrothermal method and the obtained magnetic nanocomposite was functionalized with a biocompatible, non-essential amino acid, glutamic acid, to provide functional sites. The final nanocomposite was obtained via conjugation of perhydroxycucurbit[6]uril which denoted as MFG-CB. The resulting compounds were characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), elemental analysis, vibrating sample magnetometry (VSM), the Brunauer– Emmet–Teller (BET) and zeta potential analysis. Concerning the model drug, Naringin was thereafter loaded onto the MFG-CB nanocomposite with an optimum entrapment efficiency (EE) of 98.73% and a loading capacity (LC) of 13.91%. The studies of in vitro release were conducted with regard to different pH and temperature conditions. Findings revealed the dependence of Naringin release from the nanocomposite on pH and temperature, with the maximum release achieved at pH = 5.4 at 45 °C. According to the model-dependent approach, the release mechanism was in line with the Korsmeyer-Peppas and first-order kinetic models. Finally, the in vitro cytotoxicity of the MFG-CB nanocomposite, Naringin-loaded MFG-CB was evaluated against human breast cancer (MCF-7) and human epithelial cervical cancer (HeLa) cell lines using N colorimetric assays. The results confirmed the improved cytotoxicity of Naringin by loading on the MFG-CB nanocomposite.

Significant Benefits of Environmentally Friendly Hydrosols from Tropaeolum majus L. Seeds with Multiple Biological Activities.

Tropaeolum majus L. is a traditional medicinal plant with a wide range of biological activities due to the degradation products of the glucosinolate glucotropaeolin. Therefore, the goals of this study were to identify volatiles using gas chromatography-mass spectrometry analysis (GC-MS) of the hydrosols (HYs) isolated using microwave-assisted extraction (MAE) and microwave hydrodiffusion and gravity (MHG). Cytotoxic activity was tested against a cervical cancer cell line (HeLa), human colon cancer cell line (HCT116), human osteosarcoma cell line (U2OS), and healthy cell line (RPE1). The effect on wound healing was investigated using human keratinocyte cells (HaCaT), while the antibacterial activity of the HYs was tested against growth and adhesion to a polystyrene surface of Staphylococcus aureus and Escherichia coli. Antiphytoviral activity against tobacco mosaic virus (TMV) was determined. The GC-MS analysis showed that the two main compounds in the HYs of T. majus are benzyl isothiocyanate (BITC) and benzyl cyanide (BCN) using the MAE (62.29% BITC and 15.02% BCN) and MHG (17.89% BITC and 65.33% BCN) extraction techniques. The HYs obtained using MAE showed better cytotoxic activity against the tested cancer cell lines (IC50 value of 472.61-637.07 µg/mL) compared to the HYs obtained using MHG (IC50 value of 719.01-1307.03 μg/mL). Both concentrations (5 and 20 µg/mL) of T. majus HYs using MAE showed a mild but statistically non-significant effect in promoting gap closure compared with untreated cells, whereas the T. majus HY isolated using MHG at a concentration of 15 µg/mL showed a statistically significant negative effect on wound healing. The test showed that the MIC concentration was above 0.5 mg/mL for the HY isolated using MAE, and 2 mg/mL for the HY isolated using MHG. The HY isolated using MHG reduced the adhesion of E. coli at a concentration of 2 mg/mL, while it also reduced the adhesion of S. aureus at a concentration of 1 mg/mL. Both hydrosols showed excellent antiphytoviral activity against TMV, achieving100% inhibition of local lesions on the leaves of infected plants, which is the first time such a result was obtained with a hydrosol treatment. Due to the antiphytoviral activity results, hydrosols of T. majus have a promising future for use in agricultural production.

Spectroscopic Characterization, Quantum Chemical, Molecular Docking, Antibacterial and Anticancer Studies on Ethyl Coumarin-3-Carboxylate: an Antibacterial and Lung Cancer Agent

The detailed theoretical and experimental (FT-IR, FT-Raman, UV-visible) spectroscopy analyses of the Ethyl Coumarin-3-Carboxylate (ECC) molecule were carried out. The ECC compound’s pharmacological properties were also investigated, utilizing antibacterial and anticancer activity investigations. Initially, the ECC molecule was optimized by the density functional theory B3LYP method with a 6-311 G++ (d,p) basis set using the Gaussian 09 W program. The optimized molecular structure provides the harmonic vibrational frequencies of the ECC molecule. The observed and computed vibrational wavenumbers were assigned and found to be well correlated. UV-Vis absorption spectrum analysis indicates that the molecule contains π →π* and n → π* electronic transitions. The Frontier molecular orbital analysis confirmed the molecular reactivity and bioactivity of ECC, while the Mulliken atomic charge distribution analysis pinpointed the molecule’s reactive sites. Antibacterial testing demonstrated the ECC compound’s inhibitory effect on various bacterial strains, with a particular impact on Klebsiella pneumonia. In vitro, anticancer assessments showcased ECC's stronger inhibitory effects on A549 lung cancer cell lines compared to HeLa cervical cancer cell lines. Additionally, in silico molecular docking investigations provided further validation that the ECC compound can inhibit the function of the epidermal growth factor receptor, a factor associated with lung cancer. As a result, this study lays the foundation for the development of novel drugs for lung cancer treatment.

Pro-Apoptotic Activity of Epi-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis.

Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, epi-obtusane, previously isolated from Aplysia oculifera, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential -12.3 ± 2.3), and the antiproliferative potential of epi-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. Epi-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of epi-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases.

9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins

Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25–50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.

Maackiain suppresses the development of cervical cancer via AMPK priming autophagy.

Maackiain (Mac), a flavonoid analog isolated from Sophora flavescens, exhibits neuroprotective, anti-allergic, anti-inflammatory, and pro-apoptotic effects. It is not clear whether Mac has a therapeutic effect on cervical cancer. In this work, we used RT-qPCR, western blot, immunofluorescence, and related methods to detect the therapeutic mechanism of Mac for cervical cancer. We demonstrated that Mac significantly inhibited the proliferation, migration, and invasion of human cervical cancer cell lines HeLa and SiHa. And, Mac enhanced the pro-apoptotic effects of cisplatin in treating cervical cancer cells. Mac has shown good efficacy in treating cervical cancer. Furthermore, Mac inhibited the mammalian target of the rapamycin (mTOR) pathway, thereby inducing autophagy in cervical cancer cells. The regulation of mTOR/autophagy pathway by Mac relied on the activation of AMP-activated protein kinase (AMPK), and the inhibition of the AMPK reversed the Mac's anti-cervical cancer activity. In addition, experimental study of Mac in mouse xenograft tumor model further confirmed its good anti-cervical cancer activity. Mac inhibits human cervical cancer by activating the AMPK/mTOR/autophagy pathway, indicating that it is a potential natural compound for the treatment of cervical cancer. This study also provides a feasible molecular mechanism for the treatment of cervical cancer.

ELK4 Promotes Cell Cycle Progression and Stem Cell-like Characteristics in HPV-associated Cervical Cancer by Regulating the FBXO22/PTEN Axis

Cervical cancer (CC) is a prevalent gynecological carcinoma, and patients infected with human papillomavirus (HPV) have a higher morbidity rate. To explore the effects of ETS-like transcription factor 4 (ELK4) in patients with HPV+ CC. In vitro cell lines and human-sample study. The ELK4 levels in human tissue (65 HPV+ CC tissue and 25 HPV− normal cervical tissue) and cell lines (human cervical epithelial immortalized cell line H8 and CC cell lines HeLa [HPV18], CaSki [HPV16], and SiHa [HPV−]) were quantified using qRT-PCR and western blot assay. ELK4 knockdown transfection was effective and confirmed by western blotting. The MTT and EDU assays were used to evaluate cell viability and proliferation, respectively. Flow cytometry was used to detect the CC cell cycle stage. Stem cell markers, such as cluster of differentiation 133 (CD133), CD44, and aldehyde dehydrogenase 1, and the cervicospheres formed were measured. ChIP-qPCR and luciferase activity experiments were used to assess the bond between ELK4 and F-box protein 22 (FBXO22). ELK4 was highly expressed in the HPV+ CC tissue. CC cells with ELK4 knockdown had lower viability and proliferation than the control cells. ELK4 knockdown blocked the progression of the cell cycle from G1 to S phase. ELK4 knockdown suppressed the stem cell-like characteristics of the HPV+ CC cells. ELK4 bonded with the FBXO22 promoter, inhibiting the levels of phosphatase and tensin homolog (PTEN). ELK4 facilitated cell cycle progression and stem cell-like characteristics by regulating the FBXO22/PTEN axis. Thus, ELK4 could be a potential therapeutic target to arrest the progress of HPV-associated CC.

Biological synthesis of manganese oxide nanoparticles from aerial parts of Prunus dulcis and their in vitro investigation of medical properties

The field of functional nanohybrid material is an emerging research area in material science due to its vast range of applications. The use of novel technology and innovative therapeutics has led to potent applications, including controlling the size of nanoparticles (NPs). This has resulted in a novel report on the synthesis of manganese oxide NPs using aerial parts of queen of roses Prunus dulcis (almond) leaves, seed, and seed oil (using Clevenger apparatus), which functions as a reducing agent. Manganese sulfate was used as a precursor in the synthesis process. The synthesized nanohybrid Mn3O4 NPs were studied using different characteristics techniques such as X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy‐dispersive X‐ray spectroscopy (EDX). The photoluminescence spectra display the blue emission ranging from 483.2 to 486.5 nm. The biosynthesized Mn3O4 NPs were tested for bactericidal activity and showed tremendous inhibition against gram‐positive and gram‐negative bacteria. The antioxidant activity of Mn3O4 NPs was enhanced using 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay, which revealed the higher activity of Mn3O4 NPs from P. dulcis leaf extract. In vitro cytotoxicity of hybrid Mn3O4 NPs was examined using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay against cervical cancer (HeLa cell line) with different concentrations. The results showed an IC50 value of 61.97 μg mL−1 for Mn3O4 NPs from P. dulcis leaf extract. In general, the phytosynthetic route with synergistic effect of nanohybrid demonstrated an interaction with cancer cells, highlighting a pioneering optimum approach in synthesis of Mn3O4 NPs from aerial parts of P. dulcis.

Cytotoxic Activity of Wild Plant and Callus Extracts of Ageratina pichinchensis and 2,3-Dihydrobenzofuran Isolated from a Callus Culture.

Ageratina pichinchensis (Kunth) R.M. King & H. Rob. belongs to the Asteraceae family and is a plant native to Mexico to which several biological properties are attributed. In this study, the cytotoxic effect of four extracts from the wild plants and two extracts from A. pichinchensis callus culture were evaluated against carcinogenic cell lines including prostate carcinoma, cervical cancer, hepatocellular carcinoma, hepatoma human, lung cancer, and cellular keratinocytes. The extracts were obtained with ethyl acetate and methanol using both leaves and stems or the callus. Only the ethyl acetate extract of the callus culture influenced the cervical cancer cell line (HeLa) with an IC50 of 94.79 ± 2.0 µg/mL. From the ethyl acetate callus extract, 2,3-dihydrobenzofuran was isolated and purified and also evaluated against cancer cells. The cytotoxic evaluation of this compound showed a significant effect against the HeLa cell line with an IC50 of 23.86 ± 2.5 µg/mL. Our results contribute to the development of biotechnological alternatives and extraction processes to produce compounds with possible potential against certain types of human cancer.

Detection of HPV in urine for cervical cancer screening: feasibilty of an assay system.

The detection of urine HPV is considered as a promosing alternative to increase the screening coverage of cervical cancer. However, the validated assay of urine HPV is still scarse. We described a nouvel assay syetem for the urine-based detection of HPV in the framework of HPV screening. This sytsem consisted of Automate Nimbus extraction of DNA and AnyplexTM II HPV HR Detection PCR of HPV DNA. We validated this system by spiking HPV-infected cervical cancer cell line HeLa cells into normal urine and compared the prelimary results of cervical samples and urine samples. We found that this system could detect as few as 5 HeLa cells in normal urine model. Some discordances of HPV results between cervical samples and urine samples were observed. We concluded that this assay system could be applied for the detection of HPV in urine. A Large scale study is necessary to evaluate the clinical significance of this assay system.

Formulation of Thiamine-Laden Chitosan Nanosphere for Nutraceutical Application

Introduction:: Thiamine, often known as vitamin B1, is a water-soluble vitamin that can be added to food or purchased as a supplement. It plays an important role in many cellular processes and is crucial for overall human health. The synthesis and characterization of Thiamineencapsulated chitosan nanospheres for sustained release and improved bioavailability is the major objective of this study. Materials and Methods: The chitosan nanospheres were prepared using sodium tripolyphosphate (TPP) as cross-linking agent. Results:: The ionic interactions between chitosan and TPP produced small-sized stable nanospheres for the incorporation of Thiamine. The conjugate was characterized through a UV spectrophotometer and Fourier Transform Infrared spectroscopy (FTIR). The size and morphology were determined using Zetasizer and Scanning Electron Microscopy (SEM). An average size of 504 nm size was obtained for the nanospheres. The in vitro release studies were performed for 30 days to assess the sustained release of thiamine from nanoencapsulates. Cellular uptake of the thiamine-encapsulated chitosan nanoparticles was studied in the human cervical cancer cell lines (HeLa) and mus-musculus 3T3 L1 cell lines. Conclusion:: This study is an early design and development of a technology for encapsulating water-soluble vitamins in biodegradable polymers, which can be examined for the vitamin's long-term bioavailability.

IN VITRO EVALUATION OF ANTIOXIDANT AND CYTOTOXIC ACTIVITIES ON HUMAN CERVICAL CANCER CELLS IN THREE DIFFERENT PLANT EXTRACTS FROM TURKEY

The objective of this investigation was to assess the total phenolic and flavonoid content within acetone and water extracts derived from Erica manipuliflora, Ferula communis, and Stevia rebaudiana plants. Additionally, the in vitro antioxidant and cytotoxic effects of these extracts were evaluated using the human cervical cancer (HeLa) cell line as a model. Among the three plant species examined, the highest concentrations of total phenols and flavonoids were found in the acetone extract of E. manipuliflora, measuring 365.29 mg GAE/g DW and 105.42 mg QE/g DW, respectively. Acetone and water extracts of E. manipuliflora showed higher DPPH scavenging activities (IC50: 37.57 and 33.27 µg/mL, respectively) compared to other plants. furthermore, E. manipuliflora acetone extract (IC50: 97.35 µg/mL) exhibited the highest inhibition in the HeLa cell line treated with the extracts, thus being the most effective extract on this cell line. As a result of the analyzes, it has been shown that F. communis and S. rebaudiana and especially E. manipuliflora are important natural antioxidant sources with their strong radical scavenging effects, as well as the anticancer potential of these plants.

Effect of trichostatin A on biological characteristics of side population cells of cervical cancer cell line (HeLa)

Purpose: To investigate the effect of trichostatin A (TSA) on biological characteristics of side population (SP) cells of cervical cancer cell line (HeLa)Methods: Side population (SP) and NSP cells were obtained from 6th generation of primary cervical cancer cells and cervical cancer cell line (HeLa). Cell surface markers (ATP-binding membrane transporter superfamily G member 2 (ABCG2), CD133, CD43, p63, Ki67, multidrug resistance (MDR) as well as cell cycle phase distribution and apoptosis, were determined. SP cells in HeLa were divided into 3 groups that received TSA at doses of 0.01, 0.05, and 0.2 μM. Untreated cells served as control. Cell growth inhibition rates of different dose groups were compared. SP cells in HeLa were divided into simple irradiation group and combined irradiation group TSA (10 % inhibition concentration (IC10) + irradiation, and values of SP cell survival fraction (SF) of the two groups under different irradiation conditions were compared.Results: The content of SP in HeLa cell line was significantly higher than in cervical cancer tissue (p > 0.05). There were no significant differences in expression levels of ABCG2, CD133, CD43, p63, Ki67, and MDR, as well as G0/G1, S, and G2/M phase distributions and apoptosis rate between HeLa cell line and cervical cancer tissue (p > 0.05). On the 3rd, 5th, and 7th day, SF value of SP cells was significantly higher in NSP cells (p > 0.05). With increasing concentration of TSA, SF value of NSP cells gradually decreased, while that of SP cells did not change significantly.Conclusion: Cervical cancer cell line (HeLa) contains SP cells which have biological characteristics of tumor stem cells. Moreover, TSA exerts good cytotoxicity and radio-sensitization effect on SP cells.

Lanostane triterpenoids with anti-proliferative and PTP1B/α-glucosidase inhibitory activities from the fruiting bodies of Ganoderma calidophilum

Twelve previously undescribed and four known lanostane triterpenoids were isolated from the fruiting bodies of Ganoderma calidophilum. The structures of undescribed compounds, ganodecalones H–S (1−12), were elucidated by extensive spectroscopic analysis as well as ECD and NMR calculations. Compound 4 showed significant inhibitory activity against human leukaemia cell line K562, gastric cancer cell line SGC-7901, and cervical cancer cell line HeLa with IC50 values of 13.10 ± 0.19, 17.26 ± 4.75, and 4.36 ± 0.58 μM, respectively. Compound 16 exhibited inhibitory potency against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase with IC50 values of 30.2 ± 0.13 μM and 120.6 ± 0.14 μM, respectively. The binding sites and interactions of 16 with PTP1B and α-glucosidase were revealed using molecular docking simulations.

Development and Assessment of 1,5-Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK-2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a-j, 8a-j, 9a-c, and 10a-c. The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d, 8g, 8i, and 10c inhibited EGFR with IC50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d, 8g, 8i, and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.

Half-Sandwich Iridium(III), Rhodium(III), and Ruthenium(II) Complexes Chelating Hybrid sp2-N/sp3-N Donor Ligands to Achieve Improved Anticancer Selectivity.

The biological efficacy of half-sandwich platinum group organometallic complexes of the formula [(η5-Cpx)/(η6-arene)M(XY)Cl]0/+ (XY = bidentate ligands; Cpx = functionalized cyclopentadienyl; M = Ir, Rh, Ru, Os) has received considerable attention due to the significance of the metal center, chelating ligand, and Cpx/arene moieties in defining their anticancer potency and selectivity. With a facile access to the BIAN-derived imine-amine ligands using alkylaluminum as the reductant, we herein described the preparation and characterization of 16 half-sandwich Ir(III), Rh(III), and Ru(II) complexes chelating the hybrid sp2-N/sp3-N donor ligand. A nonplanar five-member metallacycle was confirmed by X-ray single-crystal structures of Ir1-Ir3, Ir7, Rh1, Ru1, and Ru4. The attempt to prepare imine-amido complexes using a base as the deprotonating agent led to the mixture of imine-amine complexes, within which the leaving group Cl- was displaced, and 16-electron imine-amido complexes without Cl-. The half-sandwich imine-amine complexes in this system underwent rapid hydrolysis in aqueous solution, exhibited weak photoluminescence, and showed the ability of binding to CT-DNA and BSA. The cytotoxicity of all imine-amine complexes against A549 lung cancer cell lines, HeLa cervical cancer cell lines, and 4T1 mouse breast cancer cells was determined by an MTT assay. The IC50 values of these complexes were in a range of 5.71-67.28 μM. Notably, most of these complexes displayed improved selectivity toward A549 cancer cells versus noncancerous BEAS-2B cells in comparison with the corresponding α-diimine complexes chelating the sp2-N/sp2-N donor ligand, which have been shown no selectivity in our previous report. The anticancer selectivity of these complexes appeared to be related to the redox-based mechanism including the catalytic oxidation of NADH to NAD+, reactive oxygen species (ROS) generation, and depolarization of the mitochondrial membrane. Further, inducing apoptosis of these complexes in A549 cancer cells and BEAS-2B normal cells also correlated with their anticancer selectivity, indicating the apoptosis mode of cell death in this system. In addition, these complexes could enter A549 cells via energy-dependent pathway and were able to impede the in vitro migration of A549 cells.