Human Cervical Cancer Cells Research Articles

Verapamil modulates NFAT2 to inhibit tumor growth and potentiates PD1ab immune checkpoint inhibitor therapy in cervical cancer treatment

Purpose Current evidence suggests a high co-prevalence of hypertension and cervical cancer. Accordingly, blood pressure control is indicated during anti-tumor drug therapy in this patient population. Over the past few years, immunotherapy has made great strides in treating different cancers. However, the role and clinical significance of verapamil as a first-line anti-hypertensive drug during immunotherapy remain poorly understood, emphasizing the need for further studies. Methods Murine cervical cancer models were employed to assess the effect of verapamil monotherapy and combination with PD1ab. Immunohistochemistry was conducted to quantify the abundance of CD8+ T cell and Ki67+ cells. Several in-vitro and in-vivo assays were used to study the effects of verapamil and explore the preliminary mechanism. Results Monotherapy with verapamil or PD1ab immune checkpoint inhibitor significantly suppressed the growth of subcutaneously grafted U14 cells in WT BABL/c mice, respectively, with increased survival time of mice. Consistent results were observed in the melanoma model. Furthermore, we substantiated that verapamil significantly impaired tumor proliferation and migration of SiHa human cervical cancer cells in vitro and in vivo. In silico analysis using TCGA data revealed that NFAT2 expression negatively correlated with patient survival. The CCK8 assay revealed that verapamil abrogated the stimulatory effect of NFAT2 after knockdown of NFAT2. Conclusions Our results suggest that verapamil inhibits tumor growth by modulating NFAT2 expression and enhancing tumor immune responses to PD1ab, which can be harnessed for cervical cancer therapy, especially for patients with comorbid hypertension. Indeed, further clinical trials are warranted to increase the robustness of our findings.

Cytotoxicity against human cancer cells and lymphocytes based on cerium oxide nanostructures

Nanomedicine has emerged as a promising avenue for targeted cancer therapy, aiming to develop innovative approaches with improved efficacy and reduced side effects. CeO2 Nanostructures (CeO2 NSs) have attracted considerable attention in biomedical research due to their unique physicochemical properties and potential applications in cancer therapy. In the present article, we studied various methods of synthesis of biocompatible cerium oxide nanoparticles through phyto synthesis (CeO2-P) using Heritiera fomes plant extract and the chemical reducing method (CeO2-C). As obtained, CeO2-P and CeO2-C were characterized using XRD (X-ray diffraction), FTIR(Fourier Transformation Infrared spectroscopy), UV-Visible spectroscopy, and field emission scanning electron microscopy. Further, cytotoxic activity was studied on human cancer cell lines – MDA-MB-231-human breast cancer cell line; HeLa -human cervical cancer cell line; HCT-116- human colon cancer cell line, and human blood mononuclear cells (lymphocytes). A comparative study evaluating the induction of apoptosis by CeO2-P and CeO2-C was performed using propidium iodide staining on the mentioned human cancer cell lines. Toxicity assessment results showed the better performance of CeO2-P nanoparticles against HCT-116 at an IC50 concentration of 6.37 μg/mL compared to CeO2-C nanoparticles (HCT-116 - 8.08μg/mL). Similarly, the CeO2 nanoparticles showed significant cytotoxicity against Hela and MDA-MB-231 cells after 24 h treatments. Interestingly, CeO2-P nanoparticles are less toxic to human blood lymphocytes than CeO2-C nanoparticles. Furthermore, propidium iodide staining revealed the signs of apoptosis in all three human cancer cell lines treated with CeO2-P compared to CeO2-C nanoparticles. In conclusion, these findings provide valuable insights into the potential use of CeO2 nanostructures as a promising therapeutic agent in cancer treatment while exhibiting minimal toxicity towards lymphocytes. Further investigations are warranted to explore the underlying mechanisms and optimize the therapeutic efficacy of CeO2 Nanostructures for targeted cancer therapy.

Kei-apple-mediated NiO nanoparticles and biological studies: anti-inflammatory and cytotoxicity study against HeLa and HEK 293 cell lines

Nickel oxide (NiO) nanoparticles are gaining popularity in multiple fields owing to their useful properties. The application in biomedicine has been further enhanced by combining them with plant extracts that possess unique biological properties. In this report, NiO nanoparticles were synthesized by mediating the reaction process with the leaf extracts of Kei-apple (Dovyallis Caffra), a local fruit tree found in South Africa. Various characterization techniques such as x-ray diffraction (XRD), V–Vis spectroscopy (UV–Vis), transmission electron microscope (TEM), Scanning electron microscope (SEM), and Energy dispersive x-ray analysis (EDX) were employed to establish the different physicochemical properties of the prepared NiO material. The XRD report obtained confirmed the formation of NiO nanoparticles with an average crystallite size of 9 mm. Furthermore, the microscopic techniques showed that the material possessed a spherical-shaped structure, with diameter sizes smaller than 27.18 nm (average size of about 11 nm). The purity of the material was shown in the EDX analysis, in which the primary composition was only the elemental constituents of the NiO nanoparticles. The nanoparticles exhibited good cytotoxicity comparable to the 5-Fluorouracil in both the Human embryo kidney (HEK 293) and Human cervical cancer (HeLa) cell lines, with a half maximal inhibitory concentration (IC50) value of 0.00015 and 13.8 μg ml−1, respectively. The anti-inflammatory study, on the other hand, exhibited a weak anti-inflammatory effect in the used Bovine serum albumin denaturation assay. The finding here thus suggests that the Kei-apple mediated NiO nanoparticles can be safely used in different fields without causing any appreciable harm to the human body due to the specificity to the cancerous cell line and the observed weak viability in the used non-cancerous embryonic kidney cells.

Design and synthesis of indole-benzimidazole hybrid molecules and evaluation of their in-vitro cytotoxic activities

ABSTRACT. Cancer is one of the most deadly diseases worldwide, challenging the world for effective treatment of the diseases, to tackle this problem a vast amount of therapeutic candidates are being investigated. Indole-benzimidazole structures have recently gained considerable attention, because compounds containing these structure exhibit a very good anticancer property. Two series of novel indole-benzimidazole hybrids molecules viz., 2-(5-substituted-1H-indol-3-yl)-5-substituted-1H-benzo[d]imidazole 5(a-f) and 2-(5-substituted-1-(3-methylbut-2-enyl)-1H-indol-3-yl)-5-substituted-1H-benzo[d]imidazole 6(a-f) were synthesized and characterized by spectroscopic techniques. The twelve target molecules have been investigated for their in-vitro cytotoxic activity against human ovarian carcinoma cells (SKOV-3), human prostate cancer cells (PC-3), human cervical cancer cells (HeLa) and human acute monocytic leukemia cells (THP-1) using MTT assay. Compound; 2-(5-bromo-1H-indol-3-yl)-5-methyl-1H-benzo[d]imidazole (5e) was interesting with IC50 (μM) values of 23.69 (SKOV-3), 73.05 (PC-3), 64.66 (HeLa) and 39.08 (THP-1), respectively.
 
 KEY WORDS: Indole, Benzimidazole, Hybrid molecules, Anticancer activity
 
 Bull. Chem. Soc. Ethiop. 2023, 37(5), 1209-1220. 
 DOI: https://dx.doi.org/10.4314/bcse.v37i5.13

Cytotoxicity and Apoptotic Inducing Efficacy of Ctenolepsis cerasiformis Extract on Hela Cervical Cancer Cells

Introduction: Cancer is a major problem around the world. Now a day’s cervical cancer becomes the most common cause of cancer in women. The early identification and affordable drugs will help to eliminate the seriousness of cancer.
 Methods: The in vitro cytotoxicity analysis of chloroform extract of Ctenolepsis cerasiformis was undertaken by the method of MTT assay and the apoptotic activity of the chloroform extract of Ctenolepsis cerasiformis was performed by the flow cytometry analysis.
 Results: The chloroform extract of Ctenolepsis cerasiformis shown important antiproliferative action on human cervical cancer cells as compared to the normal Vero cell lines.
 Discussion: There is a need to find out the less toxic or no toxic novel anti-proliferative agent from the medicinal plant sources is paramount importance.
 Conclusion: Hence, the in vitro cytotoxicity and the apoptotic effects of the chloroform extract of Ctenolepsis cerasiformis on human cervical cancer cell lines such as HeLa cell lines were undertaken.

Pink photoluminescent nitrogen-doped graphene oxide nanosheets from Juniperus squamata roots and their cytotoxic potential against human cervical cancer cells (HeLa cells) and Plasmodium falciparum an agent of malaria: A green approach

In this paper, we reported a green synthesis of nitrogen-doped graphene oxide nanosheets (N-GONSs) from Juniperus squamata roots along with its cytotoxic potential against HeLa cells, human cervical cancer cells and Plasmodium falciparum, a causative agent of malaria in humans. The water-soluble and high fluorescent N-GONSs were synthesized by hydrothermal process using Juniperus squamata roots and ethylenediaminetetraacetic acid (EDTA), as carbon and nitrogen sources without any chemical modification. The X-ray photoelectron spectroscopy (XPS) analysis confirmed that the N-GONSs were mainly composed of carbon, oxygen and nitrogen. The synthesized N-GONSs showed pink luminescence behavior under the short wavelength at 250 nm. The viabilities of the HeLa cancer cells for N-GONSs were 76.47%, 43.98%, and 20.55% after 24 h and 48 h, and 72 h, respectively, at the concentration of 50 μg/mL. Also, N-GONSs showed moderate antimalarial activity with IC50 PF3D7 45 μg/mL. Furthermore, they were also nontoxic to VERO cells (C 1008; monkey kidney epithelial cells) up to a concentration of 100 μg/mL. The present study reflected that the N-GONSs show potential cytotoxicity against HeLa cells and Plasmodium falciparum.

Lactobacillus gasseri LGV03 isolated from the cervico-vagina of HPV-cleared women modulates epithelial innate immune responses and suppresses the growth of HPV-positive human cervical cancer cells

Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. An increasing number of retrospective studies have found the depletion of Lactobacillus microbiota in the cervico-vagina facilitate HPV infection and might be involved in viral persistence and cancer development. However, there have been no reports confirming the immunomodulatory effects of Lactobacillus microbiota isolated from cervico-vaginal samples of HPV clearance in women. Using cervico-vaginal samples from HPV persistent infection and clearance in women, this study investigated the local immune properties in cervical mucosa. As expected, type I interferons, such as IFN-α and IFN-β, and TLR3 globally downregulated in HPV+ persistence group. Luminex cytokine/chemokine panel analysis revealed that L. jannaschii LJV03, L. vaginalis LVV03, L. reuteri LRV03, and L. gasseri LGV03 isolated from cervicovaginal samples of HPV clearance in women altered the host's epithelial immune response, particularly L. gasseri LGV03. Furthermore, L. gasseri LGV03 enhanced the poly (I:C)-induced production of IFN by modulating the IRF3 pathway and attenuating poly (I:C)-induced production of proinflammatory mediators by regulating the NF-κB pathway in Ect1/E6E7 cells, indicating that L. gasseri LGV03 keeps the innate system alert to potential pathogens and reduces the inflammatory effects during persistent pathogen infection. L. gasseri LGV03 also markedly inhibited the proliferation of Ect1/E6E7 cells in a zebrafish xenograft model, which may be attributed to an increased immune response mediated by L. gasseri LGV03.

Phytochemical Screening, HPTLC Fingerprinting and Evaluation of In Vitro Cytotoxic Activity of Stem Bark Extracts of Oroxylum indicum (L.) Vent. Against Human Cervical Cancer Cells.

Oroxylum indicum, a well-known traditional medicinal plant which is used to alleviate various kinds of diseases in Asia. The study aimed to identify bioactive compounds present in O. indicum stem bark using HPTLC technique. Further, the cytotoxic effects of the plant extracts were determined against HeLa (human cervical carcinoma) cell lines. The results of the study have shown the presence of the phytoconstituents such as flavonoids, phenols, tannins and steroids. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay showed that the ethanol, methanol and water extracts of O. indicum exhibited cytotoxic effect in HeLa cell lines with IC50 values of 119, 89.43 and 114.1µg/mL, respectively against standard doxorubicin with IC50 value 3.895µg/mL. The current study suggests that the methanol extract of O. indicum may offer chemopreventive properties. However, additional research is required to isolate and characterize the specific chemical entities present in O. indicum. These studies will aid in identifying a potential lead compound that holds promise as a natural anticancer agent.

Synthesis of novel Cu(II) complexes with N2O2 ligands: Characterization, theoretical calculations, antimicrobial, antioxidant, DNA binding, and in vitro anticancer activity studies

The aim was to investigate the in vitro antimicrobial, antioxidant, cytotoxic activities and pBR322 Plasmid DNA interaction potentials of newly synthesized Schiff bases and their copper complexes. Cytotoxic activities of these compounds were determined by MTT methods in human breast cancer (MCF-7), human cervical cancer (HeLa) and mouse fibroblast (L929) cell lines. The determination of changes in oxidant and antioxidant load of the cell after application of these compounds were investigated with the aid of Rel Assay Diagnostics kits. It was found that the some of the compounds had moderate antimicrobial activity, and oxidative stress index. According to plasmid DNA interaction studies, synthesized complexes modified the tertiary structure of pBR322 plasmid DNA. The compound Bis-Napht showed the highest cytotoxic activity in HeLa, MCF-7 and L929 cells at an IC50 dose of 3 ± 1 µM, 5 ± 1 µM and 3 ± 1 µM respectively. Compound Bis-Sal was determined to have lower cytotoxic activity in L-929 cells at an IC50 dose of 106 ± 9 µM at 24 h compared to other compounds. Ligand compounds and their metal complexes were optimized on the B3LYP, HF, and M06-2x methods with the 6–31++g(d,p) basis set. Afterwards, their activities were compared against crystal structure of the BRCT repeat region from the breast cancer associated protein, (BRCA1) (PDB ID: 1JNX) and crystal Structure of CDK2 receptor of cervical cancer cell proteins (PDB ID: 4BGH). To examine the interactions occurring in more detail, Protein-Ligand Interaction Profiler analysis was performed and all chemical interactions that occurred were determined.

Design, synthesis, and anticancer activity of novel 4,6-dimorpholinyl-1,3,5-triazine compounds

Abstract A series of novel 4,6-dimorpholinyl-1,3,5-triazine derivatives 6a–6r were obtained through N-substitution and Claisen-Schmidt condensation. 1H NMR, 13C NMR, and mass spectrometry were used to characterize the molecular structures of the derivatives. The in vitro antiproliferation activity of derivatives was evaluated using the MTT assay against SW620 (human colon cancer cells), A549 (human nonsmall cell lung cancer cells), HeLa (human cervical cancer cells), and MCF-7 (human breast cancer cells). Compound 6o bearing a pyridyl group exhibited good cytotoxicity against four cancer cells, with IC50 values of 8.71, 9.55, 15.67, and 21.77 μM, sequentially. In addition, compound 6a showed some selectivity against SW620.

Preliminary Screening of in vitro Kaempferia galanga Oil for Anti-Proliferative Activities Against HeLa and MCF-7 Cell

Background Kaempferia galanga, commonly known as aromatic ginger, is a potential herb with high medicinal value and is used to treat many diseases like diabetes and asthma. Cancer is a group of diseases characterized by abnormal cells that divide uncontrollably and spread throughout the body. Nowadays, medicinal plants are used for their essential oil activities, including anti-cancerous effects. Objectives The aim of this study is to establish a method for screening in vitro oil cytotoxic effects. Materials and Methods Murashige and Skoog (MS) medium with growth regulators like benzyladenine, kinetin, indole-3-acetic acid, adenine sulfate, and naphthalene acetic acid was used for plantlet production. The in vitro regenerated plants were studied for rhizome oil extraction using Clevenger’s apparatus and gas chromatography-mass spectrometry (GC-MS) analysis, followed by their cytotoxicity study against human cervical cancer cells (HeLa) and human breast cancer cells (MCF-7) by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay. Results Upon analysis, it has been found that this medicinal plant contains ethyl-p-methoxycinnamate (EPMC) (56.41 ± 0.34%) as a vital compound in its rhizome oil. The validation of cytotoxicity in both cell lines was done by treatment with rhizome oil concentrations ranging from 6.25 to 100 µL, respectively. The IC50 value was found to be 44.18 ± 0.65 µL/mL in HeLa and 72.94 ± 0.26 µL/mL in MCF-7 cells after 24 h of incubation. Conclusion The results of this study would be helpful for this important medicinal plant to be used by pharmaceuticals in the treatment of cancer.

Design, Synthesis, and Anti-Cervical Cancer and Reversal of Tumor Multidrug Resistance Activity of Novel Nitrogen-Containing Heterocyclic Chalcone Derivatives.

This study involved the design and synthesis of 21 new nitrogen-containing heterocyclic chalcone derivatives utilizing the active substructure splicing principle, with glycyrrhiza chalcone serving as the lead compound. The targets of these derivatives were VEGFR-2 and P-gp, and their efficacy against cervical cancer was evaluated. Following preliminary conformational analysis, compound 6f ((E)-1-(2-hydroxy-5-((4-hydroxypiperidin-1-yl)methyl)-4-methoxyphenyl)-3-(4-((4-methylpiperidin-1-yl)methyl)phenyl)prop-2-en-1-one) exhibited significant antiproliferative activity against human cervical cancer cells (HeLa and SiHa) with IC50 values of 6.52 ± 0.42 and 7.88 ± 0.52 μM, respectively, when compared to other compounds and positive control drugs. Additionally, this compound demonstrated lower toxicity towards human normal cervical epithelial cells (H8). Subsequent investigations have demonstrated that 6f exerts an inhibitory impact on VEGFR-2, as evidenced by its ability to impede the phosphorylation of p-VEGFR-2, p-PI3K, and p-Akt proteins in HeLa cells. This, in turn, results in the suppression of cell proliferation and the induction of both early and late apoptosis in a concentration-dependent manner. Furthermore, 6f significantly curtails the invasion and migration of HeLa cells. In addition, 6f had an IC50 of 7.74 ± 0.36 μM against human cervical cancer cisplatin-resistant HeLa/DDP cells and a resistance index (RI) of 1.19, compared to 7.36 for cisplatin HeLa cells. The combination of 6f and cisplatin resulted in a significant reduction in cisplatin resistance in HeLa/DDP cells. Molecular docking analyses revealed that 6f exhibited binding free energies of -9.074 and -9.823 kcal·mol-1 to VEGFR-2 and P-gp targets, respectively, and formed hydrogen bonding forces. These findings suggest that 6f has potential as an anti-cervical cancer agent and may reverse cisplatin-resistant activity in cervical cancer. The introduction of the 4-hydroxy piperidine and 4-methyl piperidine rings may contribute to its efficacy, and its mechanism of action may involve dual inhibition of VEGFR-2 and P-gp targets.

An electrochemical biosensor based on CuFe PBA/MoS2 nanocomposites for stable and sensitive detection of hydrogen peroxide and carcinoembryonic antigen

An increasing number of electrochemical biosensors have been constructed to detect single bioactive substances with high sensitivity, but not multiple bioactive substances with different properties. Therefore, we incorporated Cu and Fe elements into Prussian blue to form Prussian blue analogues (PBA) to improve the electrochemical catalytic activity of Prussian blue. At the same time, MoS2 is used as the material substrate to increase the electrochemical active site of the composite. We have constructed a universal electrochemical sensing platform using composite materials (CuFe PBA/MoS2) as electrode modification materials for detecting two different types of representative cancer biomarkers, hydrogen peroxide (H2O2) and carcinoembryonic antigen (CEA). The universal electrochemical biosensor showed a significant linear response to both H2O2 and CEA with the lowest detection limits of 0.23 μM and 0.01 ng mL−1, respectively, and it had high selectivity, reproducibility, and stability. The universal electrochemical biosensor is successfully applied to detect H2O2 released from human breast cancer (MCF-7) cells and CEA expressed on the surface of human cervical cancer (HeLa) cells. The developed biosensor has potential in the dynamic detection of the flux of H2O2 and the expression level of CEA from living cells. The high sensitivity of this universal sensor provides a novel strategy for simultaneously detecting multiple cancer biomarkers.

Non-natural amino acids into LfcinB-derived peptides: effect in their (i) proteolytic degradation and (ii) cytotoxic activity against cancer cells.

The dimeric peptide 26[F]: (RRWQWRFKKLG)2-K-Ahx has exhibited a potent cytotoxic effect against breast cancer cell lines, with position 26 (F) being the most relevant for anti-cancer activity. In this investigation, six analogues of the 26[F] peptide were synthesized in which the 26th position was replaced by non-natural hydrophobic amino acids, finding that some modifications increased the resistance to proteolytic degradation exerted by trypsin or pepsin. Additionally, these modifications increased the cytotoxic effect against breast cancer cells and generated cell death mediated by apoptosis pathways, activating caspases 8 and 9, and did not compromise the integrity of the cytoplasmic membrane. Finally, it was found that the modified peptides have a broad spectrum of action, since they also have a cytotoxic effect against the HeLa human cervical cancer cell line. Peptide 26[F] was inoculated in mice by ip administration and the lethal dose 50 (LD50) was between 70 and 140 mg kg-1. While for the 26[1-Nal]: (RRWQWR-1-Nal-KKLG)2-K-Ahx peptide, a dose-response test was performed, and the survival rate was 100%. These results suggested that these peptides are safe in this animal model and could be considered as promissory to develop a treatment against breast cancer.

Stapled peptide PROTAC induced significantly greater anti-PD-L1 effects than inhibitor in human cervical cancer cells.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target immune checkpoints that suppress immune cell activity. Low efficiency and high resistance are currently the main barriers to their clinical application. As a representative technology of targeted protein degradation, proteolysis-targeting chimeras (PROTACs) are considered to have potential for addressing these limitations. We synthesized a stapled peptide-based PROTAC (SP-PROTAC) that specifically targeted palmitoyltransferase ZDHHC3 and resulted in the decrease of PD-L1 in human cervical cancer cell lines. Flow cytometry, confocal microscopy, protein immunoblotting, Cellular Thermal Shift Assay (CETSA), and MTT assay analyses were conducted to evaluate the effects of the designed peptide and verify its safety in human cells. In cervical cancer celllines C33A and HeLa, the stapled peptide strongly downregulated PD-L1 to < 50% of baseline level at 0.1 μM. DHHC3 expression decreased in both dosedependentand time-dependent manners. MG132, the proteasome inhibitor, can alleviate the SP-PROTAC mediated degradation of PD-L1 in human cancer cells. In a co-culture model of C33A and T cells, treatment with the peptide induced IFN-γ and TNF-α release in a dose-dependent manner by degrading PD-L1. These effects were more significant than that of the PD-L1 inhibitor, BMS-8. Cells treated with 0.1 μM of SP-PROTAC or BMS-8 for 4 h revealed that the stapled peptide decreased PD-L1 more effectively than BMS-8. DHHC3-targeting SP-PROTAC decreased PD-L1 in human cervical cancer more effectively than the inhibitor BMS-8.

Synthesis, characterization, and cytotoxicity analysis of selenium nanoparticles stabilized by Morchella sextelata polysaccharide

Natural bioactive molecules have been widely used as stabilizers in the functional improvement of selenium nanoparticles (SeNPs) in recent years. In this study, Morchella sextelata polysaccharide (MSP) was introduced as a novel stabilizer for the synthesis of SeNPs based on the redox system of sodium selenite and ascorbic acid. The size, morphology, stability, and anti-cancer cell activities were respectively analyzed by various methods. The results showed that the synthesized SeNPs with MSP were 72.07 ± 0.53 nm in size, red in color, spherical in shape, and amorphous in nature. MSP-SeNPs showed high scavenging activity against DPPH and ABTS radicals. And, these MSP-SeNPs exhibited a significant anti-proliferation effect on human liver (HepG2) and cervical cancer (Hela) cells in vitro, while no significant cytotoxicity against normal human kidney cells (HK−2) was observed. Moreover, the mitochondria-dependent apoptosis pathway triggered by MSP-SeNPs in HepG2 cell was identified. The expression levels of p53, Bax, cytochrome c, caspase-3 and caspase-9 were all up-regulated in HepG2 cells after MSP-SeNPs treatment, while Bcl-2 expression was down-regulated. These results suggest that MSP-SeNPs have strong potential as the food supplement for application in cancer chemoprevention.

Copolymer-Green-Synthesized Copper Oxide Nanoparticles Enhance Folate-Targeting in Cervical Cancer Cells In Vitro.

Cervical cancer is fast becoming a global health crisis, accounting for most female deaths in low- and middle-income countries. It is the fourth most frequent cancer affecting women, and due to its complexity, conventional treatment options are limited. Nanomedicine has found a niche in gene therapy, with inorganic nanoparticles becoming attractive tools for gene delivery strategies. Of the many metallic nanoparticles (NPs) available, copper oxide NPs (CuONPs) have been the least investigated in gene delivery. In this study, CuONPs were biologically synthesized using Melia azedarach leaf extract, functionalized with chitosan and polyethylene glycol (PEG), and conjugated to the targeting ligand folate. A peak at 568 nm from UV-visible spectroscopy and the characteristic bands for the functional groups using Fourier-transform infrared (FTIR) spectroscopy confirmed the successful synthesis and modification of the CuONPs. Spherical NPs within the nanometer range were evident from transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The NPs portrayed exceptional binding and protection of the reporter gene, pCMV-Luc-DNA. In vitro cytotoxicity studies revealed cell viability >70% in human embryonic kidney (HEK293), breast adenocarcinoma (MCF-7), and cervical cancer (HeLa) cells, with significant transgene expression, obtained using the luciferase reporter gene assay. Overall, these NPs showed favorable properties and efficient gene delivery, suggesting their potential role in gene therapy.

Synthesis, spectral characterization and biological investigation of new organoruthenium(II) complexes with N, X-donor (X = S, O) heterocyclic chelators

New Ru(II) arene complexes containing 2,4-dihydroxyacetophenone based Schiff bases have been synthesized and characterized with FTIR, UV–visible, 1H NMR, 13C NMR and mass spectroscopies. Spectroscopic analysis revealed that the ligands coordinated to ruthenium(II) in a monobasic bidentate fashion via azomethine nitrogen and thiolate/oxalate. Antimicrobial activities of the compounds were evaluated with two bacteria (Staphylococcus aureus and Pseudomonas aeruginosa) and two fungi (Candida albicans and Candida tropicalis). The complexes displayed better antimicrobial activity over their ligands. In addition, the ligands and the complexes were analyzed for their anticancer potential against A549 (human lung carcinoma) and HeLa (human cervical cancer) cells, in which the complexes exhibited comparable activities against A549 (IC50 value is 21 ± 1 µM (1), 18 ± 1 µM (2)) and HeLa (IC50 value is 22.1 ± 0.9 µM (1), 20 ± 1 µM (2)) with the standard drug cisplatin (IC50 value is 25 ± 1 µM (A549) and 27 ± 1 µM (HeLa)). The non-toxic nature of the compounds has been confirmed with human umbilical vein endothelial cells (HUVEC cells). The obtained results highlighted the possibility of developing ruthenium arene complexes as anticancer agents.

Folate Functionalized and Evodiamine-Loaded Pluronic Nanomicelles for Augmented Cervical Cancer Cell Killing.

Evodiamine (Evo) is a natural, biologically active plant alkaloid with wide range of pharmacological activities. In the present study Evo-loaded folate-conjugated Pluronic F108 nano-micelles (ENM) is synthesized to enhance the therapeutic efficacy of Evo against cervical cancer. ENM are synthesized, physicochemically characterized and in vitro anticancer activity is performed. The study demonstrates that ENM have nanoscale size (50.33 ± 3.09nm), monodispersity of 0.122 ± 0.072, with high drug encapsulation efficiency (71.30±3.76%) and controlled drug release at the tumor microenvironment. ENM showed dose-dependent and time-dependent cytotoxicity against HeLa human cervical cancer cells. The results of in vitro anticancer studies demonstrated that ENM have significant anticancer effects and greatly induce apoptosis as compared to pure Evo. The cellular uptake study suggests that increased anticancer activity of ENM is due to the improved intracellular delivery of Evo through overexpressed folate receptors. Overall, the designed ENM can be a potential targeted delivery system for hydrophobic anticancer bioactive compound like Evo.

Design, synthesis, antibacterial/antitumor activity and in vitro stability of novel cordycepin derivatives with unsaturated fatty acid chain

To overcome the metabolic instability of cordycepin (adenosine deaminase (ADA) metabolic deamination and plasma degradation) and obtain better bioactivity, three novel kinds of cordycepin derivatives 1a-1c containing unsaturated fatty acids including linoleic acid, arachidonic acid and α-linolenic acid, respectively, were designed and synthesized. In terms of antibacterial activity, the synthesized compounds 1a and 1c showed enhanced activity than cordycepin in the tested bacterial strains. 1a-1c also exhibited enhanced antitumor activity against four cancer cell lines (human cervical cancer cell line HeLa, human non-small cell lung cancer cell line A549, human breast cancer cell line MCF-7, and human hepatoma cell line SMMC-7721) compared with cordycepin. Notably, 1a and 1b showed better antitumor activity even compared with positive control 5-Fluorouracil (5-FU) in HeLa, MCF-7 and SMMC-7721. The cell cycle assay indicated that when compared with cordycepin, 1a and 1b could significantly inhibit the cell propagation trapped in S and G2/M phases and increase the percentage of cells trapped in G0/G1 in HeLa and A549, which might provide a synergistic antitumor mechanism evidence different from cordycepin. Last but not the least, 1a and 1b displayed improved stability both in ADA solution and mouse plasma compared with cordycepin and 1a owns a solubility of 130 μg/mL in PBS. These results offer a novel insight into the primary structure and activity relationship of how the unsaturated fatty acid chain could affect the bioactivity of cordycepin, which also represents a series of cordycepin analogs with obviously improved bioactivity and enhanced stability, therefore promoting its druggable enhancement.