Human Cervix Cancer Cells Research Articles

Development of New 5‐(Oxazol‐2‐yl)Pyrimidine Derivatives with Promising Anticancer Activities

AbstractA novel series of oxazolyl‐pyrimidine derivatives (11 a–j) have been synthesized and structures were confirmed by spectral data. The synthesized compounds were assessed for cytotoxic profile towards human cervix cancer (SiHa), lung cancer (A549), breast cancer (MCF‐7), and colon cancer (Colo‐205) cell lines by employing MTT assay and using etoposide as the positive control. The heteroaryl compounds having the terminal pyridyl (11 a) and thiazolyl (11 b) groups showed superior cytotoxic potency against cervix and lung cancer cell lines and varying methoxy substituted derivatives 11 c–11 e have excellent to good cytotoxic properties. Compound 11 a and 11 b have IC50 values in the range of 0.01±0.0034 to 0.17±0.059 μM and 0.10±0.038 to 0.66±0.077 μM respectively in the tested cell lines. The selected compounds 11 a and 11 b were studied by molecular docking to assess the binding interactions, binding energies, and possible mechanisms. The in‐silico ADME properties were calculated and all the compounds have the desired properties of drug‐like molecules. The toxicity results indicate that all the compounds are free from toxicity except 11 j, which has high tumorigenic properties. The optimized structure, energies of frontier molecular orbitals, molecular electrostatic potential, and NLO parameters for compound 11 a were determined using DFT/B3LYP level with a 6‐311++G(d,p) basis set.

Calix[4]pyrrole‐Grafted Gold Nanoparticles as a Turn‐On Fluorescence Sensor for Noxious Fungicide Dimoxystrobin and Their Anti‐Cancer Activity against the KB‐3‐1 Cell Line

AbstractA rapid and easy approach for producing very stable gold nanoparticles has been discovered. Calix[4]pyrrole tetrahydrazide (CPTAH) was utilized effectively in the synthesis of gold nanoparticles as a reducing and stabilizing agent. These functionalized AuNPs were characterized by Surface Plasmon Resonance, Transmission Electron Microscopy, Selected Area Electron Diffraction, and Energy Dispersive X‐ray techniques. CPTAH‐AuNPs possessed a particle size of 11±2 nm and are highly stable at pH 7.0 for more than 150 days. The selectivity and sensitivity of CPTAH‐AuNPs as a fungicide sensor was assessed for Metalaxyl, Mancozeb, Tebuconazole, Tricyclozole, Dimoxystrobin, Kresoxim‐methyl, and Carbendazim, amongst which Dimoxystrobin (DMX) was sensed exclusively with naked eyes by means of aggregation of CPTAH‐AuNPs with a detection limit of the order of 5 ppm using “Turn‐on” fluorescence enhancement. Additionally, the CPTAH‐AuNPs were found to be effective cytotoxic agent against the human cervix cancer cell line KB‐3‐1 with IC50 value of 64.63 μg/mL which admits the employability of CPTAH‐AuNPs in the study of development of anti‐cancer drug.

Novel Peptide from the Hydrolysate of Hybrid Sturgeon (Acipenseridae) Spinal Cord: Isolation, Identification, and Anti-proliferative Effects in Human Cervix Cancer Cells.

Anti-proliferative peptides have recently attracted attention for their excellent bioactivity and biocompatibility. In this paper, five novel anti-proliferative peptides were identified from the hydrolysate of hybrid sturgeon spinal cord (HSSC). In addition, the structure-activity relationship of the novel anti-proliferative peptides was explored. In vitro experiments indicated that the peptide "VDSVLDVVRK" presented the highest inhibition of HeLa cell growth in all samples (IC50 = 2.5 μM). VDSVLDVVRK showed a random coil secondary structure and nanomicelles in the tumor microenvironment. Transmission electron microscopy results confirmed that nanomicelles disassemble as the concentration of VDSVLDVVRK decreases. Furthermore, VDSVLDVVRK could induce HeLa cell apoptosis by increasing the expression of Cyt-c (98.65 ± 1.85%, p < 0.01) and caspase-9 (39.85 ± 1.81%, p < 0.01). In this study, the anti-proliferative mechanism of the HSSC peptide was discussed, which provided a theoretical basis for the research and development of anti-proliferative functional food.

Integration of in vitro and in silico approaches to assess three Astragalus species from Turkey flora: A novel spotlight from lab bench to functional applications

Members of the genus Astragalus have a great interest as a source of natural bioactive compounds on a scientific platform. To provide multidirectional insights into three Astragalus species (A. setulosus, A. anthylloides, and A. ovalis), the current work focused on the chemical characterization and biological properties of their extracts (aerial parts and roots). The chemical characterization of the extracts was detected by HPLC-MS/MS analysis. The biological properties were evaluated by antioxidant, enzyme inhibitory, and cytotoxic parameters. Assays for radical quenching, reducing capacity, and metal chelation were also used to evaluate antioxidant properties. To test the enzyme inhibitory effects of the extracts, cholinesterases, tyrosinase, α-amylase, and α-glucosidase were utilized as target enzymes. Two cancer cell lines, (MCF-7 (human breast cancer cell line) and HeLa (Human cervix cancer cell line), were selected to evaluate cytotoxic effects. Generally, 5- caffeoylquinic acid (2.43–283.92 μg/g extract), hyperoside (4.33–216.22 μg/g extract) and rutin (1.09–184.98 μg/g extract) were the main constituents. The extracts from aerial parts and roots of A. anthylloides showed stronger radical scavenging and reducing power abilities compared to A. setulosus and A. ovalis. The best AChE and BChE inhibitory effects were determined in the aerial parts of A. setulosus (2.18 mg GALAE/g) and roots of A. ovalis (4.76 mg GALAE/g), respectively. The extracts of A. ovalis had the highest tyrosinase inhibitory abilities. The extract from aerial parts of A. setulosus showed stronger cytotoxic effects compared to other extracts. Pearson's correlation analysis revealed that the presence of some compounds (resveratrol, p-coumaric, 5-caffeoylquinic, and ferulic acids, etc) was linked to the observed biological activities. Molecular docking was also provided for the possible interaction of enzymes as well as protein targets of the tested cell lines. Our findings provide a scientific basis for the Astragalus species, which may serve as a source of naturally occurring bioactive compounds for health-promoting applications.

Anticancer effect of Citrullus colocynthis and Capparis spinosa against human Cervix and Hepatocellular cancer cell lines

Anticancer effect of Citrullus colocynthis and Capparis spinosa against human Cervix and Hepatocellular cancer cell lines

Cytotoxic Effect of Biebersteinia multifida Alcoholic Extracts on MCF-7, HeLa, and A2780 Cell Lines.

Conventional cancer treatments are costly and have different serious side effects for patients. Natural herbal treatments are widely accepted among people because of their minimal side effects, although there is little scientific knowledge about them. One of these remedies utilizes the root of Biebersteinia multifidi that has been used for years in Iran to treat different chronic genital diseases. The current study examined the effects of methanolic and ethanolic extracts of B. multifida (induction of necrosis and apoptosis) on breast cancer (MCF-7), ovarian cancer (A2780), and human cervix cancer (HeLa) cell lines in comparison with normal breast cells. These effects were determined to be morphological alterations in cell light microscopy, by flow cytometry (staining with annexin V and propidium iodide), and by measuring live cells and inhibition concentrations by MTT assay. IC50 of B. multifida on the MCF-7 cell line (methanolic extract) was 400 µg/ml and for A2780 was 250 µg/ml. The IC50 amount of B. multifida on the MCF-7 cell line (ethanolic extract) was 750 µg/ml and 1500 for A2780. Results demonstrated that apoptosis and necrosis occurred in MCF-7 and A2780 following the addition of ethanolic and methanolic extracts of B. multifida to the medium. These findings confirmed the anti-cancer effects of mehthanolic extracts of Biebersteinia multifida root and its safety for normal cells; thus, it can be applied in cancer therapy as a novel medication.

Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells.

This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“preventive protocol”; IC50 = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (“curative protocol”; IC50 = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC50 values were significantly lower than those attained in bidimensional HeLa cells (IC50 = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC50 from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC50 doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41–85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment.

Etanol ve Dimetil Sülfoksidin Çeşitli İnsan Hücre Hatları Üzerindeki in vitro Sitotoksik Etkisi

Although the cytotoxic effects of ethanol and dimethyl sulfoxide (DMSO) on some cell lines have been shown in the literature, there is no study about the cytotoxic effects of these solvents on common used human cell lines, such as melanoma (VMM917), lung cancer (A549), colon cancer (WiDr), normal colon (CCD 841 CoN) and fibroblast (BJ) cells. The aim of this study was to determine the cytotoxic effects of ethanol and DMSO on human breast (MCF-7), liver (HepG2) and cervix (HeLa) cancer cells in addition to above mentioned cells. For this purpose, the cells were treated with different concentrations (0.1%, 0.2%, 0.4%, 0.6%, 0.8%, 1%, 2%, and 4%, v/v) of ethanol and DMSO and then subjected to MTT assay. According to the results, ethanol and DMSO exhibited dose-dependent cytotoxicity in all cells studied. The most DMSO and ethanol sensitive cells were WiDr and VMM917, while the most resistant cells were determined as BJ and A549, respectively. The results revealed that the concentration range in which ethanol and DMSO exhibited cytotoxic effect in each cell line is different. In order not to cause false positive and negative results, the concentration range in which the solvents used in cell culture studies do not have cytotoxic effects should be determined.

Tri N-Heterocyclic Carbene Trinuclear Silver(I) complexes: Synthesis and In Vitro cytotoxicity studies

Synthesis of ethylene linked tris benzimidazolium bromide salts that serve as precursors for the tri-NHC ligands in the respective tri-NHC trinuclear silver(I) complexes is described (NHC = N-heterocyclic carbene). Different wingtip substituents were selected (benzyl, n-butyl, cyclopentyl, 2-methylene benzonitrile, n-decyl) to furnish five new tris benzimidazolium salts (1-5) and the respective tri-NHC trinuclear silver(I) complexes (6-10). The synthesized and characterized compounds (1-10) were evaluated for their cytotoxic potential on human colon, human breast and human epitheloid cervix cancer cell lines by determining their IC50 values and evaluating their antiproliferative activity against the selected cell lines. The tested compounds were found to be good anticancer agents against breast cancer and cervical cancer cell lines and selectively good anticancer agents for the human colon cancer cell line.

An EPR Study Using Cyclic Hydroxylamines To Assess The Level of Mitochondrial ROS in Superinvasive Cancer Cells.

It has been proposed that a mitochondrial switch involving a high mitochondrial superoxide production is associated with cancer metastasis. We here report an EPR analysis of ROS production using cyclic hydroxylamines in superinvasive SiHa-F3 compared with less invasive SiHa wild-type human cervix cancer cells. Using the CMH probe, no significant difference was observed in the overall level of ROS between SiHa and SiHa-F3 cells. However, using mitochondria-targeted cyclic hydroxylamine probe mitoTEMPO-H, we detected a significantly higher mitochondrial ROS content in SiHa-F3 compared with the wild-type SiHa cells. To investigate the nature of mitochondrial ROS, we overexpressed superoxide dismutase 2, a SOD isoform exclusively localized in mitochondria, in SiHa-F3 superinvasive cells. A significantly lower signal was detected in SiHa-F3 cells overexpressing SOD2 compared with SiHa-F3. Despite some limitations discussed in the paper, our EPR results suggest that mitochondrial ROS (at least partly superoxide) are produced to a larger extent in superinvasive cancer cells compared with less invasive wild-type cancer cells.

Cytotoxic activity against breast cancer cells of two species of marine sponges from shallows of Yucatan peninsula

This study aimed to evaluate the in vitro activity of extracts of two marine sponge species, occurring in the shallows of the Yucatan peninsula coast, on two cancer and one normal mammalian cell lines. Hexane, dichloromethane, ethyl acetate and methanol extracts of Halichondria magniconulosa and Halichondria melanadocia were screened for their cytotoxic activity against hormone-dependent breast cancer (MCF-7) and human cervix cancer (SiHa) cell lines. The ethyl acetate extract of H. magniconulosa exhibited significant cytotoxicity against MCF-7 cells to a CC50 of 0.8 µg/mL, as well as high selectivity (SI = 24.5). On the other hand, SiHa cells were moderately sensitive to the dichloromethane and ethyl acetate extracts of the same species. (CC50 = 34.9 and 31.5 µg/mL, respectively). None of the extracts of H. melanadocia were considered active due their CC50’s were ranged from 59.0 to 94.5 µg/mL.

Apoptosis-inducing activity of safflower (Carthamus tinctorius L.) seed oil in lung, colorectal and cervix cancer cells

Carthamus tinctorius L. (Safflower) has been often preferred because of rich fatty acid, flavonoid, alkaloid, and polysaccharide contents in its different parts in medicine and industrial area. Although its antioxidant, antienflamatuar, and antitumor properties have been proven in many studies, the mechanism underlying the anticancer activity is still more unclear. This study was first conducted to elucidate the apoptotic gene expression changes in human colorectal (CaCo-2), lung (A549), and cervix cancer (HeLa) cells after exposure to safflower seed oil (SFO). Cytotoxic activity of cancer cells was evaluated by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl2H-tetrazoliumbromide) assay and then, total RNA derived from cell lines to analyze the gene expression profile on Real-Time Ready Human Apoptosis Panel 96 was used. MTT results showed that SFO greatly inhibited A549, CaCo-2 and HeLa cell proliferation, with a value of IC50 of 1.26, 3.92 and 13.12 μg/ml, respectively. According to the cDNA microarray analysis, 56 genes were interpreted in connection with extrinsic, intrinsic, PI3K/AKT, JAK/STAT, and NFκB pathways. SFO treatments triggered apoptosis through the caspase-dependently pathway along with upregulated the expressions of many pro-apoptotic genes in the extrinsic and intrinsic pathway in HeLa cells. However, in A549 and CaCo-2 cells, SFO treatments were inhibited cell survival mechanism through frequently caspase-independent genes following downregulated the expression of anti-apoptotic genes. It is noteworthy that although cancer cells have different sensitivity, SFO induced apoptosis through different pathways. Taken together, SFO, as a natural resource, has the potential to be used as a promising agent against cancer, especially in gene therapy level.

An In Vitro Study on the Interactions of Pycnogenol® with Cisplatin in Human Cervical Cancer Cells.

In the treatment of cancer, it is intended to increase the anticancer effect and decrease cytotoxicity using various plant-derived phenolic compounds with chemotherapeutic drugs. Pycnogenol® (PYC), a phenolic compound, has been the subject of many studies. Since the mechanisms of the interactions of PYC with cisplatin need to be clarified, we aimed to determine the effects of PYC on cisplatin cytotoxicity in human cervix cancer cells (HeLa) and to evaluate the genotoxicity of PYC. The cytotoxicity of cisplatin and PYC was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa cells for 24 h and 48 h. The effect of PYC against oxidative DNA damage was evaluated using the comet assay. The IC50 values of cisplatin were 22.4 μM and 12.3 μM for 24 h and 48 h, respectively. The IC50 values of PYC were 261 μM and 213 μM for 24 h and 48 h, respectively. For 24 h exposure, PYC significantly reduced the IC50 value of cisplatin at the selected concentrations (15.6-500 μM). For 48 h exposure, PYC did not change the cytotoxicity of cisplatin at concentrations between 15.6 and 125 μM, but significantly reduced it at concentrations of 250 μM and 500 μM. PYC alone did not induce DNA damage at concentrations of 10 μM or 25 μM; however, it significantly induced DNA damage at higher concentrations (50-100 μM). It also significantly reduced H2O2-induced DNA damage at all concentrations studied (10-100 μM). Our results suggest that PYC may increase the cisplatin cytotoxicity in HeLa cells at nongenotoxic doses. The results might contribute to the anticancer effect of cisplatin with PYC in cervical carcinoma, but in order to confirm this result further in vitro studies with cancer cell lines and in vivo studies are needed.

Structural architectures and biological properties of main group bismuth(III) iodide complexes with heterocyclic thioamides

A series of mononuclear, dinuclear and polynuclear bismuth(III) iodide complexes (1–5) bearing heterocyclic thioamide ligands, 2-mercapto-3,4,5,6-tetrahydro-pyrimidine (tHPMT), 2-mercapto-benzimidazole (MBZIM), 2-mercapto-1-methylimidazole (MMI), 2-mercaptobenzothiazole (MBZT) and 2-mercaptopyridine (PYT), have been synthesized and characterized by melting point, elemental analysis, FT-IR spectroscopy, Raman spectroscopy, 1H, 13C NMR spectroscopy, UV–Vis spectroscopy and Thermal Gravimetry-Differential Thermal Analysis (TG-DTA). Moreover, the crystal structures of 1–5 have been also determined with single crystal X-ray diffraction analysis. The use of the above mentioned heterocyclic thioamide ligands have allowed synthesis of the first examples of bismuth(III) iodide thioamide complexes. {[BiI3(tHPMT)3]} (1) is the first structural example of a neutral mononuclear bismuth(III) iodide complex with octahedral geometry around the bismuth(III) ion with meridional conformation. {[BiI2(µ2-I)(MBZIM)2]2} (2) is the first example of a dinuclear bismuth(III) iodide complex with octahedral geometry around the bismuth(III) ion with trans-S/cis-I arrangement. {[BiI(µ2-I)2(MMI)]n} (3) and {[BiI(µ2-I)2(MBZT)]n·CH3OH} (4) are the first examples of the polynuclear bismuth(III) iodide complexes with octahedral geometry around the bismuth(III) ions. The ligand molecules are coordinated via the thione sulfur atoms in both complexes but in complex 3, ligand molecules are trans to each other in polymeric chain while, in complex 4, ligand molecules are cis to each other in polymeric chain. {[BiI(µ2-S,N-PYT)2]n} (5) is the first example of a polynuclear bismuth(III) iodide complex with pentagonal bipyramidal geometry around the bismuth(III) ions. The seven coordinate bismuth(III) atom has a N2S4I-donor set consisting of one iodine atom and two chelating and bridging μ2-S,N (η2-S:η1-N) pyridine-2-thionate anions.Complexes 1–5 were evaluated for their in vitro cytotoxic activity against human adenocarcinoma cervix (HeLa) and breast (MCF-7) cancer cells. The toxicity of the complexes was studied against human fetal lung fibroblast cells (MRC-5). The influence of 1–5, upon the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX), was evaluated experimentally.

Dorycnium pentaphyllum Extract Has Antiproliferative Effect on Human Cervix and Colon Cancer Cells

Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin–Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract’s cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.

Synthesis, spectral analysis, antimicrobial, cytotoxicity, and antioxidant studies of gold(III) complex of caffeine

In the present study, the reactions involving caffeine (CA) and gold(III) were investigated. The synthesized complex was characterized by using mass, UV–visible, FTIR, 1H and 13C NMR, and TG-DTA analyses. From these analyses, it is predicted that the complex has the formula [Au(CA)2(Cl)2]Cl. In addition, antimicrobial, cytotoxicity, and antioxidant activities of the obtained complex were investigated. Investigation of antimicrobial properties demonstrated that the complex has important antibacterial and antifungal activities. The cytotoxic activity of the complex showed potent cytotoxicity against growth of human prostate (Du145), cervix (HeLa), colon (HT29), and breast (MCF7) cancer cells. Additionally, the complex showed significant antioxidant activity.

Synthesis, characterization, theoretical and cytotoxicity studies of Pd(II) and Pt(II) complexes with new bidentate carbon donor ligand

The new phosphonium salt, the C,C-chelating phosphorus ylide ligand, (MeOC6H5C(O)CHPPh2(CH2)2PPh2CHC(O)C6H5OMe), and its Pd(II) and Pt(II) complexes have been synthesized and the cytotoxic activity of the synthesized complexes against three human cancer cell lines, including HeLa (Human cervix cancer cell line), KB (human oral cancer cell line) and U87 MG (human glioblastoma cell line) were evaluated using an MTT assay. The new compounds were identified and characterized using multinuclear (1H, 13C and 31P) NMR, infrared (IR) spectroscopy, elemental analysis, and through UV absorption and fluorescence emission spectra. Also, the crystal structure of the phosphorus ylide ligand was determined by single-crystal X-ray diffraction analysis. According to the obtained results from the MTT assay, the Pd(II) and Pt(II) complexes demonstrated a higher cytotoxic activity against KB human oral cancer cells in comparison with other cell lines, rendering these compounds into suitable candidates for further anti-oral cancer studies. Furthermore, a theoretical study on structure and nature of the MC bonding between the Y ligand (ylide) and MCl2 fragment in the [YMCl2] (M = Pd, Pt and Y = (MeOC6H5C(O)CHPPh2(CH2)2PPh2CHC(O)C6H5OMe)) complexes have been reported via NBO and energy-decomposition analysis (EDA).

Mutant p53R248Q downregulates oxidative phosphorylation and upregulates glycolysis under normoxia and hypoxia in human cervix cancer cells.

Mutations in p53 are strongly associated with several highly malignant cancer phenotypes but its role in regulating energy metabolism has not been completely elucidated. The effect on glycolysis and oxidative phosphorylation (OxPhos) of mutant p53R248Q overexpression in HeLa cells (HeLa-M) was analyzed and compared with cells overexpressing wild-type p53 (HeLa-H) and nontransfected cells containing negligible p53 levels (HeLa-L). p53 R248Q overexpression induced early cell detachment during in vitro growth; however, detached HeLa-M cells showed high viability, shorter generation time and significant diminution in the adhesion proteins E-cadherin and β-catenin versus HeLa-H and HeLa-L cells. Under normoxia, a lower growth rate of attached HeLa-M cells correlated with decreased levels of proliferating cell nuclear antigen (PCNA), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), adenosine monophosphate-activated protein kinase (AMPK), mitochondrial proteins (20-80%) and OxPhos flux (69 ± 12%). On the contrary, HeLa-M also showed increased contents of CDKN1A, nuclear factor κB (NF-κB), c-MYC, hypoxia-inducible factor 1-α (HIF-1α; 1-4 times), glycolytic HIF-1α targets (2-4 times), and glycolysis flux (2-fold) versus HeLa-H. In consequence, glycolysis provided ~70% of the cellular adenosine triphosphate (ATP) in HeLa-M cells under normoxia whereas, OxPhos predominated (65-82%) in HeLa-H and HeLa-L cells. Pifithrin-α, a specific p53 inhibitor, did not alter the p53 R248Q target protein contents and OxPhos and glycolytic fluxes, and a poor HIF-1α-p53 R248Q interaction was attained, in HeLa-M cells. These observations suggested that p53 R248Q deficiently interacted with pifithrin-α and HIF-1α. Therefore, lower mitochondrial biogenesis, deficient HIF-1α/mutant p53 interaction, and development of a pseudohypoxic state under normoxia were the apparent biochemical mechanisms underlying glycolysis activation and OxPhos downregulation in HeLa-M cells.

CXCL5, the upregulated chemokine in patients with uterine cervix cancer, in vivo and in vitro contributes to oncogenic potential of Hela uterine cervix cancer cells

CXCL5 is showed a surprisingly elevated profile and implicated in tumorigenesis in several tumors. However, the expression and function of CXCL5 in uterine cervix cancer (UCC) remain largely unknown. The current study aimed to elucidate the expression pattern of CXCL5 in human UCC tissues and Hela cervix cancer cell, as well as its functions in Hela cells. Our data showed that CXCL5 and its receptor CXCR2 were expressed by Hela uterine cervix cancer cells. CXCL5 was upregulated in UCC tissues, and its overexpression was positively correlated with age, but did not correlate with clinical stages and tumor infiltration. Exogenous administration of CXCL5 and CXCL5 overexpression contributed to proliferation and migration activities of Hela cells in vitro, consistent with this, CXCL5 overexpression also promoted growth of Hela cells in a nude mouse xenograft model. At the gene level, CXCL5 overexpression regulated the expression of tumor-related genes including ERK, p-ERK, AKT, p-AKT, DIABOL, NUMB, NDRG3 and CXCR2. Taken together, CXCL5 may contribute to a dominant role in UCC progression and sever as a potential molecular therapeutic target for UCC.

Primula vulgaris extract induces cell cycle arrest and apoptosis in human cervix cancer cells

Primula vulgaris belongs to the genus Primula, members of which are frequently used in folk medicine. Various studies have investigated the cytotoxic effect of different Primula species, but there have been limited studies on the cytotoxic effect of P. vulgaris. The aim of this study was to investigate the cytotoxic effects, and possible mechanisms involved, of P. vulgaris flower extract on human cervical cancer (HeLa) cells. The cytotoxic effect of the extract on HeLa cells was revealed using the MTT assay. Mechanisms involved in the extract's cytotoxic effect were then investigated in terms of apoptosis, mitochondrial membrane potential, and the cell cycle, using fluorometric methods. P. vulgaris flower extract exhibited selective cytotoxic effects against HeLa cells by arresting their cell cycle at the S phase, and inducing the number of apoptotic cells compared to normal fibroblast cells by reducing mitochondrial membrane potential in a concentration-dependent manner. This is the first study to reveal the antiproliferative effect of P. vulgaris flower extract. Further studies are now needed to identify the cytotoxic molecules in the extract and their mechanisms.