Growth Of HeLa Cells Research Articles

Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity.

Ellagic acid (EA) is present at relatively high concentrations in many berries and has many beneficial health effects, including anticancer properties. To improve the development and utilization of blackberry fruit nutrients, we divided Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW. Single-factor tests and response surface methodology were used to optimize the extraction process, while macroporous resin adsorption and alkali dissolution, acid precipitation, and solvent recrystallization were used for purification. The highest purity of the final EA powder was 90%. The anticancer assessment results determined by MTT assay showed that EA inhibited HeLa cells with an IC50 of 35 μg/mL, and the apoptosis rate of the cells increased in a dose-dependent manner, with the highest rate of about 67%. We evaluated the changes in the mRNA levels of genes related to the EA-mediated inhibition of cancer cell growth and initially verified the PI3K/PTEN/AKT/mTOR pathway as the pathway by which EA inhibits HeLa cell growth. We hope to provide a theoretical basis for the deep exploration and utilization of this functional food.

Structural and Thermomagnetic Properties of Gallium Nanoferrites and Their Influence on Cells In Vitro.

Magnetite and gallium substituted cuboferrites with a composition of GaxFe3-xO4 (0 ≤ x ≤ 1.4) were fabricated by thermal decomposition from acetylacetonate salts. The effect of Ga3+ cation substitution on the structural and thermomagnetic behavior of 4-12 nm sized core-shell particles was explored by X-ray and neutron diffraction, small angle neutron scattering, transmission electron microscopy, Mössbauer spectroscopy, and calorimetric measurements. Superparamagnetic (SPM) behavior and thermal capacity against increasing gallium concentration in nanoferrites were revealed. The highest heat capacity typical for Fe3O4@Ga0.6Fe2.4O4 and Ga0.6Fe2.4O4@Fe3O4 is accompanied by a slight stimulation of fibroblast culture growth and inhibition of HeLa cell growth. The observed effect is concentration dependent in the range of 0.01-0.1 mg/mL and particles of Ga0.6Fe2.4O4@Fe3O4 design have a greater effect on cells. Observed magnetic heat properties, as well as interactions with tumor and healthy cells, provide a basis for further biomedical research to use the proposed nanoparticle systems in cancer thermotherapy (magnetic hyperthermia).

Cytotoxic activity of Galantamine hydrobromide against HeLa cell line

Cytotoxic activity of Galantamine HBr against human cervical adenocarcinoma cell line HeLa in different concentrations (1.875 μМ ÷ 30 μМ) was evaluated. Inhibition of HeLa cell growth after treatment with Galantamine HBr and index of cell viability were determined. From the experimental results was proven that the drug exerts cytotoxic activity towards HeLa cell line, with antiproliferative activity presented as the value of IC50 = 30 μM ± 0.22.

Nona-Arginine Mediated Anti-E6 ShRNA Delivery Suppresses the Growth of Hela Cells in vitro.

The E6 oncoprotein of HPV plays a crucial role in promoting cell proliferation and inhibiting apoptosis, leading to tumor growth. Non-viral vectors such as nona-arginine (R9) peptides have shown to be potential as carriers for therapeutic molecules. This study aimed to investigate the efficacy of nona-arginine in delivering E6 shRNA and suppressing the E6 gene of HeLa cells in vitro. HeLa cells carrying E6 gene were treated with a complex of nona-arginine and E6 shRNA. The complex was evaluated using gel retardation assay and FESEM microscopy. The optimal N/P ratio for R9 peptide to transfect HeLa cells with luciferase gene was determined. Relative real-time PCR was used to evaluate the efficiency of mRNA suppression efficiency for E6 shRNA, while the effect of E6 shRNA on cell viability was measured using an MTT assay. The results indicated that R9 efficiently binds to shRNA and effectively transfects E6 shRNA complexes at N/P ratios greater than 30. Transfection with R9 and PEI complexes resulted in a significant toxicity compared to the scrambled plasmid, indicating selective toxicity for HeLa cells. Real-time PCR confirmed the reduction of E6 mRNA expression levels in the cells transfected with anti-E6 shRNA. The study suggests that R9 is a promising non-viral gene carrier for transfecting E6 shRNA in vitro, with significant transfection efficiency and minimal toxicity.

Differential association of hedgehog pathway in development of cervical carcinoma and its chemo-tolerance

Cervical carcinoma (CACX) is still a dreadful threat to women in developing countries. Available conventional chemo-radiation therapies are not sufficient to restrict the disease recurrence. To unravel the mechanism of the disease recurrence, alteration of hedgehog self-renewal pathway was evaluated during development of CACX and in chemo-tolerance of the tumor. We have analyzed the alterations (expression/methylation/deletion) of some key regulatory genes (HHIP/SUFU/SHH/ SMO/GLI1) of hedgehog self-renewal pathway in cervical lesions at different clinical stages and compared with different datasets, followed by their clinico-pathological correlations. The changes in expression/methylation of the genes were then evaluated in two CACX cell lines (SiHa/HeLa) after treatment with chemotherapeutic drug cisplatin at different concentrations. Down regulation (mRNA/protein) of the antagonists HHIP and SUFU due to promoter methylation and/or deletion along with upregulation (protein) of agonists SHH, SMO and GLI1 was seen in early invasive lesions and subsequent clinical stages. Reduced protein expression of HHIP and SUFU showed significant association with high/intermediate expression of agonists SHH, SMO, GLI1 in the tumors and also poor prognosis of the patients. It was evident that cisplatin could restrict the growth of HeLa and SiHa cells through significant upregulation of antagonists HHIP and SUFU due to their promoter hypomethylation and down regulation of SHH in a concentration dependent manner without any significant changes in expression of SMO and GLI1, leading to the tumor cells in a dormant state. Thus, interplay of the agonists and antagonists has important role in activation of hedgehog pathway during development of CACX, whereas inactivation of the pathway due to upregulation of the antagonists is an important phenomenon in chemo-tolerance of the tumor. This suggests importance of epigenetic modification in chemo-resistance of CACX.

Biogenic Nanoparticles: Synthesis, Characterization, and Biological Potential of Gold Nanoparticles Synthesized using Lasiosiphon eriocephalus Decne Plant Extract.

Recent advancements in biomedicine have revolutionized nanomedicine as a therapeutic moderator in the management of both infectious and noninfectious diseases. In the current study we demonstrated biosynthesis of gold nanoparticles using aqueous leaf extract of Lasiosiphon eriocephalus as a capping and reducing agent and evaluation of their antioxidant, antibacterial, and anticancer properties. The biosynthesized LE-AuNPs were characterized by UV-Vis spectrophotometry, SEM, TEM, XRD, FTIR, DLS, and Zeta potential analysis. The antibacterial activity was checked by a minimum inhibitory concentration assay. The anticancer potential of biogenic LE-AuNPs was checked by cytotoxicity and genotoxicity assay against HeLa and HCT-15 cells. The characteristic surface plasmon resonance peak of the colloidal solution at 538 nm by UV-Vis spectrum confirmed the formation of LE-AuNPs in the solution. The SEM, TEM, and XRD revealed 20-60 sized hexagonal and crystalline LE-AuNPs. The LE-AuNPs displayed significant inhibition potential against DPPH and ABTS radicals in vitro. The LE-AuNPs demonstrated significant antibacterial potential. The results of cytotoxicity interpreted that biogenic gold nanoparticles exhibited strong dose and time-dependent cytotoxicity effect against selected cancer cell lines where IC50 of LE-AuNPs required to inhibit the growth of HeLa cells after 24 h and 48 h exposure were 5.65± 0.69 μg/mL and 4.37±0.23 μg/mL respectively and that of HCT- 15 cells was 6.46 ± 0.69 μg/mL and 5.27 ± 0.34 μg/mL, 24h and 48h post-exposure respectively. Findings from this study revealed that gold nanoparticles synthesized using L. eriocephalus, showed remarkable antioxidant, antimicrobial, and extensive cytotoxicity and genotoxicity activities.

Natural Gallic Acid and Methyl Gallate Induces Apoptosis in Hela Cells through Regulation of Intrinsic and Extrinsic Protein Expression.

Induction of apoptosis is one of the targeted approaches in cancer therapies. As previously reported, natural products can induce apoptosis in in vitro cancer treatments. However, the underlying mechanisms of cancer cell death are poorly understood. The present study aimed to elucidate cell death mechanisms of gallic acid (GA) and methyl gallate (MG) from Quercus infectoria toward human cervical cancer cell lines (HeLa). The antiproliferative activity of GA and MG was characterised by an inhibitory concentration using 50% cell populations (IC50) by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Cervical cancer cells, HeLa, were treated with GA and MG for 72 h and calculated for IC50 values. The IC50 concentration of both compounds was used to elucidate the apoptotic mechanism using acridine orange/propidium iodide (AO/PI) staining, cell cycle analysis, the Annexin-V FITC dual staining assay, apoptotic proteins expressions (p53, Bax and Bcl-2) and caspase activation analysis. GA and MG inhibited the growth of HeLa cells with an IC50 value of 10.00 ± 0.67 µg/mL and 11.00 ± 0.58 µg/mL, respectively. AO/PI staining revealed incremental apoptotic cells. Cell cycle analysis revealed an accumulation of cells at the sub-G1 phase. The Annexin-V FITC assay showed that cell populations shifted from the viable to apoptotic quadrant. Moreover, p53 and Bax were upregulated, whereas Bcl-2 was markedly downregulated. Activation of caspase 8 and 9 showed an ultimate apoptotic event in HeLa cells treated with GA and MG. In conclusion, GA and MG significantly inhibited HeLa cell growth through apoptosis induction by the activation of the cell death mechanism via extrinsic and extrinsic pathways.

Olive: A Potential Suppressor for Cervical Cancer by Upregulation of P21.

Background Cervical cancer is the second deadliest for women between the ages of 20 and 39 years. Even with prevention tactics for screening, incident rates and mortality of cervical cancer remain high. Olive has been shown to have many beneficial effects in humans concerning cardiovascular disease and inflammation. Despite these promising benefits, little is known about its effect on cervical cancer. This study examined the effects and mechanism of effects of olive extract (OE) on the HeLa cervical cancer cell line. Methodology We utilized clonogenic survival assay, quick cell proliferation assay, and caspase-3 activity to investigate the effect of OE on the proliferation and apoptosis of the cervical cancer cell line HeLa. To investigate the mechanisms behind these findings, Reverse transcription polymerase chain reaction and immunohistochemistry were performed. Results OE inhibited the growth and proliferation of HeLa cells. In comparison to the control, the percentage of colonies, as well as the optical density of the cervical cancer cells, was found to be decreased. In addition, the relative activity of caspase-3, a marker for apoptosis, was increased after treatment with OE. The anti-proliferative effect of OE on HeLa cells correlated with the increase of an anti-proliferative molecule p21. However, the pro-apoptotic effect of OE was not correlated with the change in major pro-apoptotic or anti-apoptotic molecules examined in this study. Conclusions Our study suggests that OE inhibits the growth of HeLa cervical cancer cells by upregulation of p21. Further investigation of the effects of OE on cervical cancer and other cancers is warranted by these results.

Methylselenocysteine Promotes Etoposide Cytotoxicity by Enhancing Homotypic Gap Junctions Composed of Connexin 26

To investigate the effect of methylselenocysteine (MSC) on the function of homotypic gap junction (GJ) composed of connexin (Cx) 26 and its regulation of chemotherapeutic drug cytotoxicity. The Tet-on HeLa cells transfected with and stably expressing Cx26 were used as the tool cells. Effects of MSC on cell growth, GJ function, and Cx26 protein expression were examined by MTT method, parachute assay, and Western blot analysis, respectively. The cytotoxicity of chemotherapeutic drugs was determined by standard colony-forming assay, and the relationship between MSC's effect on cytotoxicity of these chemotherapeutic drugs and its regulation of GJ was further analyzed. In Tet-on HeLa cells, doxycycline (Dox) can induce the expression of Cx26, which could then form functional GJs. Within a concentration range of 50 μmol/L, MSC had no significant effect on HeLa cell growth. Non-toxic concentrations of MSC can enhance GJs in a concentration-dependent manner and exert its effect at the nanomolar level. This effect was associated with an induction of Cx26 protein expression by MSC. Among the three common chemotherapeutic agents with different mechanisms of action, etoposide (Eto) presented cytotoxicity differences between HeLa cells cultured at low density (nonconfluent, no GJ formed) and high density (confluent, GJ formed). What's more, the inhibitory effect of Eto combined with MSC on HeLa cell colony formation was stronger than that of Eto alone, and this effect occurred only in HeLa cells with GJ formation. MSC can potentiate the cytotoxicity of Eto by enhancing the GJs composed of Cx26, indicating that combined strategy of selenide and chemotherapy shows potential value in the treatment of malignant tumors.

Hydrazinecarbonyl-thiazol-2-acetamides with pronounced apoptotic behavior: synthesis, in vitro/in vivo anti-proliferative activity and molecular modeling simulations

A new series of N-[4-(2-substituted hydrazine-1-carbonyl)thiazole-2-yl]acetamides was synthesized and evaluated in vitro against six human cell lines as antitumor agents. Compounds 20, 21 and 22 showed remarkable inhibition to HeLa (IC50 values of 1.67, 3.81, 7.92 µM) and MCF-7 (IC50 values of 4.87, 5.81, 8.36 µM, respectively) cell growth with high selectivity indices and safety profiles. Compound 20 showed significant decreases in both tumor volume and body weight gain compared to vehicle control, in the solid tumor animal model of Ehrlich ascites carcinoma (EAC) with recovered caspase-3 immuno-expression. Flow cytometry cell analysis showed that 20 exerts anti-proliferative activity in mutant Hela and MCF-7 cell lines through arresting the cell growth at the G1/S phase producing cell death via apoptosis rather than necrosis. To explain the antitumor mode of action of the most active compounds, EGFR-TK and DHFR inhibition assays were carried out. Compound 21 conveyed dual EGFR/DHFR inhibition with IC50 0.143 (EGFR) and 0.159 (DHFR) µM. Compound 20 showed DHFR inhibition with IC50 0.262 µM. Compound 22 exhibited the best EGFR inhibitory efficacy with IC50 0.131 µM. Molecular modelling study revealed that 21 and 22 have binding interactions with EGFR amino acid residues Lys745 and Asp855. Compounds 20 and 21 showed affinity toward DHFR amino acid residues Asn64, Ser59 and Phe31. The ADMET profile and Lipinski’s rule of five calculated for these compounds were acceptable. Compounds 20, 21 and 22 could be regarded as promising prototype antitumor agents for further optimization.

In vitro analysis of green synthesized CuO nanoparticles using Tanacetum parthenium extract for multifunctional applications.

Tanacetum parthenium L. is a popular traditional medicinal plant that the role of presence of particular phytochemical compounds are still unconsidered particularly in the bio-nano researches. Here, for the first time, the green fabrication of CuO NPs using Tanacetum parthenium L. extract was performed and assessed for the antimicrobial, cytotoxicity, and dye degradation activities. Characterization of CuO NPs was done by UV-visible spectra, XRD, FT-IR, TEM, and EDX. The synthesized CuO NPs possess a crystalline nature, a functional group that resembles T. parthenium, with a spherical shape particle with an average size of 28nm. EDX confirmed CuO NPs formation. The CuO NPs showed excellent antimicrobial activity against tested microorganisms. The cytotoxicity of CuO NPs was demonstrated the concentration-dependent inhibition of the growth against both cancer and normal cell lines. The results exhibited concentration-dependent inhibition of the growth of Hela, A 549, and MCF7 cancer cells (IC50 = 65.0, 57.4, and 71.8µg/mL, respectively), which were statistically significant comparing control cells (IC50 = 226.1µg/mL). Furthermore, we observed that CuO NPs-induced programmed cell death in the cancer cells were mediated with the downregulation of Bcl2 and upregulation of bax, caspase-3. CuO NPs were verified to be a superb catalyst as they had excellent activity for the degradation of 99.6%, 98.7%, 96.6%, and 96.6% of Congo red, methylene blue, methylene orange, and rhodamine B as industrial dyes in 3, 6.5, 6.5, and 6.5min, respectively. Overall, the present study nominates T. parthenium as a proper bio-agent in the biosynthesis of CuO NPs with powerful catalytic and antimicrobial activities as well as a cancer treatment.

Biogenic Synthesis of Silver Nanoparticles using Lasiosiphon eriocephalus (Decne): In vitro Assessment of their Antioxidant, Antimicrobial and Cytotoxic Activities.

The emergence of novel nanobiomedicine has transformed the management of various infectious as well as non-infectious diseases.Lasiosiphon eriocephalus, a medicinal plant, revealed the presence of active secondary metabolites and biological potentials. The present study was aimed to demonstrate the biosynthesis of silver nanoparticles using L. eriocephalus leaf extract (LE-AgNPs) and their biological properties, such as antioxidant, antibacterial and anticancer potential. The biosynthesized LE-AgNPs were characterized by UV-Visible spectroscopy, Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR) analysis. The antibacterial activity was checked by minimum inhibitory concentration (MIC) and zone of inhibition assays against Gram-positive and Gram-negative bacteria. The anticancer potential of biogenic LE-AgNPs was checked by cytotoxicity and genotoxicity assay against human cervical adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cells. UV-visible spectroscopy confirmed the formation of silver nanoparticles by measuring the surface plasmon resonance peak of the colloidal solution at 410-440 nm. The results of SEM and TEM revealed the distribution and spherical shape of 20-50 nm sized AgNPs. XRD spectrum confirmed the characteristic peaks at the lattice planes 110, 111, 200, 220 and 311 of silver which confirmed the crystalline nature of biosynthesized LE-AgNPs. FTIR spectrum of plant extract and biogenic LE-AgNPs was recorded in between 1635-3320 cm-1 which confirmed stretching vibrations of possible functional groups C=C and O-H, responsible for the reduction of silver ions to silver nanoparticles. The in vitro antioxidant potential of LE-AgNPs was evaluated using DPPH (IC50 = 26.51 ± 1.15 μg/mL) and ABTS radical assays (IC50 =74.33 ± 2.47 μg/mL). The potential antibacterial effects of LE-AgNPs confirmed that 92.38 ± 2.70% growth inhibition occurred in E. coli in response to 0.1mg/mL concentration of LE-AgNPs followed by P. aeruginosa (75.51 ± 0.76), S. aureus (74.53 ± 1.26) and K. pneumoniae (67.4 ± 3.49). The cytotoxicity results interpreted that the biogenic silver nanoparticles exhibited strong dose and time dependent cytotoxicity effect against selected cancer cell lines where IC50 concentration of LE-AgNPs required to inhibit the growth of HeLa cells after 24 h exposure was 4.14 μg/mL and MCF7 cells 3.00 μg/mL, respectively. Significant DNA fragmentation was seen in the DNA extracted from HeLa and MCF-7 cells exposed to more than 2.5 to 10 μg/mL concentrations of LE-AgNPs. The overall findings from the present investigation indicated that the AgNPs synthesized using L. eriocephalus exerted strong biological potentials such as antioxidant, antimicrobial and extensive cytotoxicity and genotoxicity activities.

A co-delivery system based on chlorin e6-loaded ROS-sensitive polymeric prodrug with self-amplified drug release to enhance the efficacy of combination therapy for breast tumor cells.

Background: Recently, various combination therapies for tumors have garnered popularity because of their synergistic effects in improving therapeutic efficacy and reducing side effects. However, incomplete intracellular drug release and a single method of combining drugs are inadequate to achieve the desired therapeutic effect. Methods: A reactive oxygen species (ROS)-sensitive co-delivery micelle (Ce6@PTP/DP). It was a photosensitizer and a ROS-sensitive paclitaxel (PTX) prodrug for synergistic chemo-photodynamic therapy. Micelles size and surface potential were measured. In vitro drug release, cytotoxicity and apoptosis were investigated. Results: Ce6@PTP/DP prodrug micelles exhibited good colloidal stability and biocompatibility, high PTX and Ce6 loading contents of 21.7% and 7.38%, respectively. Upon light irradiation, Ce6@PTP/DP micelles endocytosed by tumor cells can generate sufficient ROS, not only leading to photodynamic therapy and the inhibition of tumor cell proliferation, but also triggering locoregional PTX release by cleaving the thioketal (TK) bridged bond between PTX and methoxyl poly (ethylene glycol). Furthermore, compared with single drug-loaded micelles, the light-triggered Ce6@PTP/DP micelles exhibited self-amplified drug release and significantly greater inhibition of HeLa cell growth. Conclusion: The results support that PTX and Ce6 in Ce6@PTP/DP micelles exhibited synergistic effects on cell-growth inhibition. Thus, Ce6@PTP/DP micelles represent an alternative for realizing synergistic chemo-photodynamic therapy.

Nanoemulsion Composed of α-Tocopherol Succinate and Dequalinium Shows Mitochondria-Targeting and Anticancer Effects.

Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic delivery are detailed in many nanoemulsion studies and show the tremendous potential of targeted delivery to inhibit cancer cell growth. Dequalinium (DQA) and α-tocopherol succinate (α-TOS) are good agents for targeting mitochondria. In this study, we aimed to develop a mitochondria-targeting emulsion, using DQA and α-TOS (DTOS), for cancer treatment. DTOS emulsions of 150-170 nm in diameter were formulated using homogenization. DQA and α-TOS were used as bifunctional agents (surfactants) to stabilize the nanoemulsion and anticancer drugs. Various molar ratios of DQA and α-TOS were tested to determine the optimal condition, and DTOS 5-5 was selected for further study. The DTOS emulsion showed improved stability, as evidenced by its ability to remain stable for three years at room temperature. This stability, combined with its effective targeting of mitochondria, led to inhibition of 71.5% of HeLa cells after 24 h. The DTOS emulsion effectively inhibited spheroid growth in the 3D model, as well as prevented the growth of HeLa cells grafted onto zebrafish larvae. These results highlight the DTOS emulsion's promising potential for mitochondria-targeting and cancer treatment.

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.

Emodin Exhibits Strong Cytotoxic Effect in Cervical Cancer Cells by Activating Intrinsic Pathway of Apoptosis

Pharmacognosy Research,2022,14,4,499-503.DOI:10.5530/pres.14.4.72Published:October 2022Type:Original ArticleAuthors:Amir Saeed, and Ahmed Alharbi Author(s) affiliations:Amir Saeed1,2, Ahmed Alharbi1 1Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, KSA. 2Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Medical Sciences and Technology, Khartoum, SUDAN. Abstract:Background: Cervical cancer is widely acknowledged as the main cause of mortality and a major obstacle to increasing life expectancy, after breast cancer, in women. Natural products have been proven to be a promising source for the development of potential anticancer drugs. Emodin (1,3,8-trihydroxy-6-methyl-9,10-anthracenedione) is shown to exert wide range of biological effects, including antibacterial, hepatoprotective, anti-inflammatory and anticancer. Aim: The major aim of this study was to evaluate the efficacy of emodin against the progression of human cervical cancer. Materials and Methods: The cytotoxic effect of emodin on cervical cancer HeLa cells was assessed by cell viability assay and phase contrast microscopy. Moreover, DAPI staining was performed to analyze nuclear condensation. H2DCFDA staining was done to evaluate ROS generation. Activation of caspases was determined to ascertain mitochondria-mediated apoptosis in cervical cancer cells. Results: The results revealed that emodin strongly inhibited the HeLa cell growth and proliferation; which was validated by cell viability assay and phase contrast microscopy. Moreover, DAPI staining authenticated nuclear condensation and fragmentation in HeLa cells indicating initiation of apoptosis. We also observed significant ROS generation and caspases activation in emodin-treated cervical cancer cells. Conclusion: Our results suggested strong cytotoxic potential of emodin against cervical cancer cells. Keywords:Apoptosis, Cervical Cancer, DAPI, Emodin, HeLa, ROSView:PDF (807.5 KB)

Synthesis and catalytic performance of banana cellulose nanofibres grafted with poly(ε-caprolactone) in a novel two-dimensional zinc(II) metal-organic framework

In this study, banana cellulose nanofibres (BNCFs) were prepared using waste banana stems. A novel two-dimensional (2D) Zn-MOF was synthesized using 5-(1-hydro-imidazolyl) isophthalic acid as the ligand. The results of the X-ray diffraction, thermogravimetry, and scanning electron microscopy analyses confirmed the stability of Zn-MOF. Thus, Zn-MOF was used to catalyze BNCFs grafted with poly(ε-caprolactone) (ε-CL) (BGCL) by homogeneous ring-opening polymerization in ionic liquid. The grafting ratio of the BGCL prepared by Zn-MOF reached 84.12 %, which was 10.03% higher than that catalyzed by 4-dimethylamino pyridine which was the state-of-the-art catalyst for this reaction. The banana cellulose nanofibres grafted with ε-CL reactions followed the coordination-insertion mechanism, which was confirmed by the theoretical calculations using the Materials Studio software. The cytotoxicity results indicated that BGCL was not only non-toxic to Hela cells but also promoted Hela cell growth within a certain concentration range. Therefore, this study demonstrated the promising potential of BGCL for biomedical applications, and the high efficiency, non-toxicity, and stability of Zn-MOF as the catalyst. Further, this will provide a theoretical basis for the application of MOFs as catalysts in polymerization reactions.

Local anesthetic lidocaine induces growth suppression of HeLa cells by decreasing and changing the cellular localization of the proliferation marker Ki-67.

Although surgery is a basic therapy for cancer, it causes inflammation and immunosuppression, often resulting in recurrence and metastasis. Previous studies have suggested that anesthetic management influences the prognosis of cancer surgery patients. Administration of local anesthetics, such as lidocaine, for pain control reportedly improves their clinical outcomes; however, the precise underlying mechanism has not been fully elucidated. The growth of human embryonic kidney (HEK) 293T and cervical cancer HeLa cells was inhibited by lidocaine treatment and these cell lines showed different sensitivities for lidocaine. Ki-67 is a significant prognostic marker of cancer because it is expressed in the nucleus of actively proliferating cells. In lidocaine-treated HeLa cells, Ki-67 was detected not only in the nucleus but also in the cytoplasm. In addition, lidocaine-induced cytoplasmic Ki-67 partly colocalized with the increased ER chaperone, glucose-regulated protein 78, which is crucial for protein folding and maintenance of cellular homeostasis. Furthermore, lidocaine decreased Ki-67 levels and increased the population of HeLa cells in the G0/G1 phase. These results indicate that lidocaine plays a significant role in growth suppression by regulating the expression and distribution of Ki-67.

α-Pinene inhibits the growth of cervical cancer cells through its proapoptotic activity by regulating the miR-34a-5p/Bcl-2 signaling axis.

Among gynecological tumors, cervical cancer (CC) has the second-highest prevalence and mortality rate. α-Pinene is a bicyclic monoterpenoid compound extracted from pine needles that carried promising anticancer properties. Nevertheless, its effect on CC and the underlying mechanism has not yet been elucidated. Therefore, we investigated the effect of α-Pinene on apoptosis in CC via in vitro assays of flow cytometry (FCW), terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL) assay, quantitative real-time polymerase chain reaction(qRT-PCR), and Western blot. Following that, we detected the proapoptotic function of α-Pinene on HeLa cells in vivo by TUNEL assay and immunofluorescence staining. Our results displayed that the α-Pinene inhibited the growth of HeLa cells and stalled the cells in the G0/G1 phase. Interestingly, we also detected that α-Pinene induced HeLa cells to apoptosis. The results investigated that α-Pinene induced HeLa cells apoptosis along with up-regulating the expression of Bax, Bid, caspase-9, caspase-3, miR-34a-5p, and down-regulating the expression of Bcl-2 in vitro. At the same time, the expression levels of target genes in vivo were consistent with those in vitro. Our experiment proved that α-Pinene promoted apoptosis, which will be used to hopefully maximize the therapeutic strategies in clinical studies in CC.

New alkaloids and their in vitro antitumor activity of Corydalis balansae

The chemical investigation on Corydalis balansae resulted in the isolation of three previous undescribed compounds (1, 10, and 11) and 17 known compounds. Compound 1 and 2 were obtained as two lignanamide dimers, and compound 11 had a spiro [benzofuranone-benzazepine] skeleton, which was found in Corydalis for the first time. The structures of new compound were determined by the detailed analysis of 1D/2D NMR, UV, and IR data. Absolute configurations of compounds 10 and 11 were defined by their crystal X-ray diffraction data and calculations of electronic circular dichroism (ECD). The CCK-8 method was used to assay the inhibition effect of all the compounds on the growth of Hela, MGC-803, A549, and HepG2 cancer cells. Compound 2, 13, and 14 showed moderate inhibitory activity against the tested cell lines. Compound 2 exhibited potential antitumor activity against MGC-803 cells with an IC50 value of 20.8 μM, while the positive control etoposide was 17.3 μM. Furthermore, results from the cellular-mechanism investigation indicated that compound 2 could induce S-phase cell-cycle arrest and MGC-803 cells apoptosis, which was triggered by the up-regulation of PARP1, caspase-3 and -9, Bax, and down-regulation of Bcl-2. The 2-induced strong apoptosis indicated that compound 2 had good potential as an antitumor lead compound.