Human Cervical Cancer HeLa Cells Research Articles

CD44 Receptor-Mediated/Reactive Oxygen Species-Sensitive Delivery of Nanophotosensitizers against Cervical Cancer Cells.

Stimulus-sensitive, nanomedicine-based photosensitizer delivery has an opportunity to target tumor tissues since oxidative stress and the expression of molecular proteins, such as CD44 receptors, are elevated in the tumor microenvironment. The aim of this study is to investigate the CD44 receptor- and reactive oxygen species (ROS)-sensitive delivery of nanophotosensitizers of chlorin e6 (Ce6)-conjugated hyaluronic acid (HA) against HeLa human cervical cancer cells. For the synthesis of nanophotosensitizers, thioketal diamine was conjugated with the carboxyl group in HA and then the amine end group of HA-thioketal amine conjugates was conjugated again with Ce6 (Abbreviated as HAthCe6). The HAthCe6 nanophotosensitizers were of small diameter, with sizes less than 200. Their morphology was round-shaped in the observations using a transmission electron microscope (TEM). The HAthCe6 nanophotosensitizers responded to oxidative stress-induced changes in size distribution when H2O2 was added to the nanophotosensitizer aqueous solution, i.e., their monomodal distribution pattern at 0 mM H2O2 was changed to dual- and/or multi-modal distribution patterns at higher concentrations of H2O2. Furthermore, the oxidative stress induced by the H2O2 addition contributed to the disintegration of HAthCe6 nanophotosensitizers in morphology, and this phenomenon accelerated the release rate of Ce6 from nanophotosensitizers. In a cell culture study using HeLa cells, nanophotosensitizers increased Ce6 uptake ratio, ROS generation and PDT efficacy compared to free Ce6. Since HA specifically bonds with the CD44 receptor of cancer cells, the pretreatment of free HA against HeLa cells decreased the Ce6 uptake ratio, ROS generation and PDT efficacy of HAthCe6 nanophotosensitizers. These results indicated that intracellular delivery of HAthCe6 nanophotosensitizers can be controlled by the CD44 receptor-mediated pathway. Furthermore, these phenomena induced CD44 receptor-controllable ROS generation and PDT efficacy by HAthCe6 nanophotosensitizers. During in vivo tumor imaging using HeLa cells, nanophotosensitizer administration showed that the fluorescence intensity of tumor tissues was relatively higher than that of other organs. When free HA was pretreated, the fluorescence intensity of tumor tissue was relatively lower than those of other organs, indicating that HAthCe6 nanophotosensitizers have CD44 receptor sensitivity and that they can be delivered by receptor-specific manner. We suggest that HAthCe6 nanophotosensitizers are promising candidates for PDT in cervical cancer.

Structural Characterization, DFT, Molecular Docking and Cytotoxic Studies of Metal (II) Complexes Derived from Thiosemicarbazide

Co(II), Ni(II) and Cu(II) complexes of N and O donor ligand derived from ,5-dinitrosalicylicacid and thiosemicarbazide, the spectroscopy techniques like UV-Visible, FT-IR, NMR, mass spectrometry, p-XRD and SEM analysis were used to structurally characterize the metal complexes. From the analytical and spectral evidence, the square planar and octahedral geometry has been proposed to metal (II) complexes. In addition to this computational density functional theory (DFT) using B3LYP/6-31Gþ(d, p)/Lanl2dz(f) method in the ground state was performed, the calculations were done to confirm the geometry of the complexes and also HOMO-LUMO excitation energies levels were also calculated. Additionally, MTT test was used to perform cytotoxic assays on selected MCF-7 (estrogen receptor-positive human breast cancer cells) and HeLa (human cervical cancer cell line) cell lines. The antibacterial test was performed via the disc plate method against Escherichia coli and Staphylococcus aureus, and was further supported by molecular docking interactions using protein receptor SEC2 (PDB code: 1STE) in Staphylococcus aureus.

Lack of tumorigenesis and protumorigenic activity of human umbilical cord mesenchymal stem cells in NOD SCID mice

BackgroundThe tumorigenesis of infused umbilical cord mesenchymal stem cells (UC-MSCs) is being preclinically evaluated.MethodsWe observed tumor formation in NOD SCID mice after a single subcutaneous injection of hUC-MSCs and the effect of these cells on tumor growth in tumor-bearing mice. Three generations (P5, P7, and P10) of hUC-MSCs (1 × 107) from two donors (hUC-MSC1 and hUC-MSC2) were inoculated subcutaneously into NOD SCID mice. Subcutaneous transplantation models were established in NOD SCID mice with human cervical cancer HeLa cells (solid tumor) and human B cell lymphoma Raji cells (hematological tumor). Then, the animals were euthanized, gross dissection was performed, and tissues were collected. Various organs were observed microscopically to identify pathological changes and tumor metastasis.ResultsIn the tumorigenesis experiment, no general anatomical abnormalities were observed. In the tumor promotion experiment, some animals in the HeLa groups experienced tumor rupture, and one animal died in each of the low- and medium-dose hUC-MSC groups. The results may have occurred due to the longer feeding time, and the tumor may have caused spontaneous infection and death. Pathological examination revealed no metastasis to distant organs in any group. In the Raji tumor model, some animals in each group experienced tumor rupture, and one animal in the medium-dose hUC-MSC group died, perhaps due to increased tumor malignancy. Thus, hUC-MSCs neither promoted nor inhibited tumor growth. No cancer cell metastasis was observed in the heart, liver, spleen, lungs, kidneys or other important organs, except that pulmonary venule metastasis was observed in 1 animal in the model group.ConclusionsInjected hUC-MSCs were not tumorigenic and did not significantly promote or inhibit solid or hematological tumor growth or metastasis in NOD SCID mice.

A Review on the Morphology, Nutritional Value, Traditional Uses, Phytochemistry, and Biological Activities of Pycnarrhena cauliflora and Its Synonyms

The leaves of Pycnarrhena cauliflora, locally known as ‘pokok Ajinomoto’, are consumed as flavour enhancers by East Malaysian communities. The plant also plays a significant role in traditional medicine especially to treat snake bites, eye irritation, headache, and seizures. An extensive literature search on the species revealed that besides taxonomic description as well as toxicity against HeLa human cervical and breast cancer cell lines, there is no report on the plant chemistry. The species has nevertheless been classified as the synonym of several other species which are Antitaxis cauliflora Miers., Pycnarrhena longifolia, (Decne. ex Miq.), Antitaxis longifolius (Decne. ex Miq.) Mier., and Gabila longifolia (Decne. ex Miq, B). Among these synonyms, the plant is closely related to the species P. longifolia. Thus, a complete review of P. cauliflora and its synonyms is important to revise and evaluate its potential for further studies and commercialisation. The information on the species was collected from scientific journals, books, and reports searched through available databases such as Google Scholar, PubMed, Directory of Open Access Journals, Science Direct, Bioline International and Reaxys. This review provides an insight on the morphology, nutritional value, traditional uses, phytochemistry, and biological activities of P. cauliflora and its synonyms published between 1981 to 2021 in scientific journals, books, and reports.

Transcriptomics Reveals the Mevalonate and Cholesterol Pathways Blocking as Part of the Bacterial Cyclodipeptides Cytotoxic Effects in HeLa Cells of Human Cervix Adenocarcinoma

The incidence of human cervix adenocarcinoma (CC) caused by papillomavirus genome integration into the host chromosome is the third most common cancer among women. Bacterial cyclodipeptides (CDPs) exert cytotoxic effects in human cervical cancer HeLa cells, primarily by blocking the PI3K/Akt/mTOR pathway, but downstream responses comprising gene expression remain unstudied. Seeking to understand the cytotoxic and anti-proliferative effects of CDPs in HeLa cells, a global RNA-Seq analysis was performed. This strategy permitted the identification of 151 differentially expressed genes (DEGs), which were either up- or down-regulated in response to CDPs exposure. Database analysis, including Gene Ontology (COG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed differential gene expression on cancer transduction signals, and metabolic pathways, for which, expression profiles were modified by the CDPs exposure. Bioinformatics confirmed the impact of CDPs in the differential expression of genes from signal transduction pathways such as PI3K-Akt, mTOR, FoxO, Wnt, MAPK, P53, TGF-β, Notch, apoptosis, EMT, and CSC. Additionally, the CDPs exposure modified the expression of cancer-related transcription factors involved in the regulation of processes such as epigenetics, DNA splicing, and damage response. Interestingly, transcriptomic analysis revealed the participation of genes of the mevalonate and cholesterol biosynthesis pathways; in agreement with this observation, total cholesterol diminished, confirming the blockage of the cholesterol synthesis by the exposure of HeLa cells to CDPs. Interestingly, the expression of some genes of the mevalonate and cholesterol synthesis such as HMGS1, HMGCR, IDI1, SQLE, MSMO1, SREBF1, and SOAT1 was up-regulated by CDPs exposure. Accordingly, metabolites of the mevalonate pathway were accumulated in cultures treated with CDPs. This finding further suggests that the metabolism of cholesterol is crucial for the occurrence of CC, and the blockade of the sterol synthesis as an anti-proliferative mechanism of the bacterial CDPs, represents a reasonable chemotherapeutic drug target to explore. Our transcriptomic study supports the anti-neoplastic effects of bacterial CDPs in HeLa cells shown previously, providing new insights into the transduction signals, transcription factors and metabolic pathways, such as mevalonate and cholesterol that are impacted by the CDPs and highlights its potential as anti-neoplastic drugs.

Synthesis and biological evaluation of xanthone derivatives as anti-cancer agents targeting topoisomerase II and DNA

Topoisomerase is one of the most important targets of anti-cancer drugs. In order to develop effective and low-toxic topoisomerase inhibitors, a series of xanthone derivatives have been designed and synthesized using the principles of skeleton transition. In vitro cytotoxicity assays of human breast cancer (MCF-7), gastric cancer (MGC-803), and cervical cancer(Hela) cell lines, most of the compounds showed antitumor growth activity, and also showed low toxicity to human normal cells L929. In the enzyme activity inhibition experiment, compounds 7d and 8d showed the best inhibitory activity. The DNA binding studies disclosed that the most potent compounds 7d and 8d can intercalate into DNA, induce apoptosis in MGC-803 cells and arrest cells in G2/M phase. Molecular docking showed that compounds 7d and 8d could bind with topoisomerase II and DNA through hydrogen bonds and π-stacking interactions. Graphical abstract

Co-delivery nanosystem of Epigallocatechin Gallate and Rutin for anticancer and antibacterial activities

Although chemotherapy has successfully treated cancer to some extent, high doses, multiple drug resistance, undesirable toxic effects, and non-selective targeting are the major pitfalls. Nano drug materials have emerged as a promising method to improve the therapeutic benefit for extremely hydrophobic drugs, and nano-based combination therapy can potentially target these challenges. Here, an amphiphilic PEG-PCL diblock copolymer co-encapsulated with epigallocatechin-3-gallate and rutin nanorods within the range of 110 ± 15 nm and 26 ± 5.3 nm in length and width was developed as a combination therapy that synergistically combines features of anticancer and antibacterial activities. The drug release kinetics revealed that drug release from nanorods is due to anomalous diffusion with 77% of EGCG and 62% of rutin at lower pH 5.0 for a time period of 24 h. In vitro cytotoxicity assays against A549 human lung adenocarcinoma and HeLa cervical cancer cell lines showed that nanorods have a concentration-dependent synergistic effect in inducing intracellular reactive oxygen species (ROS) generation and cancer cell apoptosis by the up-regulation of caspase 9/3 activities. Confocal laser scanning microscopy further confirmed the potential internalization of nanorods into the cancer cells. Also, nanorods showed antibacterial effects against E. coli and S. aureus strains by cell membrane damage confirmed by time-killing kinetic studies and SEM analysis. Besides, hemolytic studies showed the biocompatibility of nanorods with human red blood cells. These findings hold promise for engineering multifunctional nanorods-based co-delivery systems targeting cancer and bacterial infections.

Matrine exerts antitumor activity in cervical cancer by protective autophagy via the Akt/mTOR pathway in vitro and in vivo.

Matrine is a quinazoline alkaloid extracted from Sophora flavescens. The aim of the present study was to determine whether matrine can induce autophagy in the human HeLa and SiHa cervical cancer cell lines in vitro and in vivo. Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of HeLa and SiHa cells. A total of 28 4-week-old female BALB/c nude mice were used for the in vivo study. Autophagy and protein expression were observed via transmission electron microscopy, monodansylcadaverine and immunohistochemical staining and western blotting. The inhibitory effect of matrine on the proliferation of cervical cancer cells was time- and dose-dependent. The combination of matrine and cisplatin synergistically inhibited the proliferation of cervical cancer cells in vitro and in vivo. Transmission electron microscopy showed that after the addition of matrine, numerous autophagosomes and autophagolysosomes were observable in HeLa and SiHa cells, as demonstrated by monodansylcadaverine staining. Western blotting and immunohistochemical staining showed that as the concentration of matrine increased, the expression of the autophagy marker LC3A/B-II also increased significantly in vitro and in vivo. These findings suggested that matrine inhibited the proliferation of cervical cancer cells and induced autophagy by inhibiting the Akt/mTOR signaling pathway. Thus, matrine may represented a potential candidate in combination therapy for cervical cancer as an inducer of autophagy.

Sdy-1 Executes Antitumor Activity in HepG2 and HeLa Cancer Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway.

Demethylincisterol A3 (Sdy-1), a highly degraded sterol that we previously isolated from Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp. HQD-6, exhibits potent antitumor activity towards a variety of cancer cells. In this study, we further verified that Sdy-1 effectively inhibited the proliferation and migration of human liver (HepG2) and cervical cancer (HeLa) cells in vitro and it can induce cell apoptosis and arrest the cell cycle in the G1-phase. Mechanistically, we demonstrated that Sdy-1 executes its function via inhibition of the Wnt/β-catenin signaling pathway. Sdy-1 may not inhibit the Wnt signaling pathway through the cascade reaction from upstream to downstream, but directly acts on β-catenin to reduce its transcription level, thereby reducing the level of β-catenin protein and further reducing the expression of downstream related proteins. The possible interaction between Sdy-1 and β-catenin protein was further confirmed by molecular docking studies. In the nude mouse xenograft model, Sdy-1 can also significantly inhibit tumor growth. These results indicated that Sdy-1 is an efficient inhibitor of the Wnt signaling pathway and is a promising antitumor candidate for therapeutic applications.

Anti-proliferative activity of in vitro Zingiberaceae essential oil against Human cervical cancer (HeLa) cell line

In many developing countries cancer is one of the main reasons of worldwide death after cardiovascular diseases. India is one of the leading producers of aromatic essential oils in the world. The family Zingiberaceae is used as a spice ingredient from centuries and as traditional medicine in Asian regions. At present there are many medicinal plants belonging to this family which are used for its aromatic oils bearing numerous beneficial effects for health maintenance including anticancer activity. In the present study we have used four plant species like Curcuma longa, Curcuma aromatica, Kaempferia galanga and Hedychium coronarium which was assessed against Human cervical cancer (HeLa) cancer cell line by MTT assay. To validate the cytotoxicity activity, HeLa cell line was treated against different concentrations of rhizome essential oils ranging from 6.25-100 ul respectively. This study revealed that Hedychium coronarium essential oil was most significantly active in comparison to other oil samples tested against HeLa cell line. Hence the cytotoxic study of essential oils could be used by pharmaceuticals and other industry for therapeutics.

The First tetrafluorinated azobenzene-imidazolium ionic conjugates as potential thermotropic liquid crystalline drugs: Self-assembly properties and cytotoxic effects

A new series of tetrafluorinated azobenzene-imidazolium ionic liquid crystals (ILCs) of varying alkyl chain length (n = 10–18 in even parity) in the imidazolium cationic head group was prepared and characterized using FTIR and NMR spectroscopy, and elemental microanalysis. Their thermal and phase properties were investigated using differential scanning calorimetry (DSC) and polarized optical microscope (POM). Their phase properties and morphology were influenced by fluorination and alkyl chain length. Long alkyl chains were necessary to induce liquid crystalline behaviour in these salts. All homologues were mesogenic, exhibiting stable smectic A phase with broad temperature range. Cytotoxic effects of these ILCs against human cervical cancer (HeLa) cells and normal fibroblasts was evaluated using the MTT assay. Cytotoxicity of these ILCs was dependent on the alkyl chain length in the imidazolium cationic head. All the salts were less toxic towards normal fibroblasts and exhibited 7–27-fold enhancement in cytotoxicity against HeLa cells (24hr IC50 ranged between 0.61 µM -2.84 µM) as compared to the standard therapeutic drug, Etoposide (IC50 = 25.67 µM). Long homologues (n = 16, 18) were selective towards cancer cells with selectivity index ≥ 3. These thermotropic ILCs could be doped with room-temperature mesomorphous polymers for the formulation of safe and selective anticancer drugs.

Synthesis and Antitumor Activity of Erlotinib Derivatives Linked With 1,2,3-Triazole.

Cervical cancer is one of the most important cause of cancer-related death and presents a major public health problem in many countries. To search for more novel antitumor agents against cervical cancer, 14 erlotinib-linked 1,2,3-triazole compounds were designed, synthesized, and evaluated for their anti-tumor activity. The compounds were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra (HR MS). Antitumor activity assay results indicated that six of those compounds have remarkable inhibitory activity against human cervical cancer HeLa cells in vitro, among which compound 4m was the most potent with IC50 of 3.79 μM, and compounds 4k, 4i, 4l, 4d, and 4n also demonstrated remarkable antitumor activity with IC50 of 3.79, 4.16, 4.36, 7.02, and 8.21 μM. We found three of the most potent compounds 4d, 4k, and 4l induced potent apoptosis and cell cycle arrest in HeLa cells, and compounds 4d and 4l significantly restrained the cell colony formation and showed moderate epidermal growth factor receptor (EGFR) inhibitory activity with IC50 of 13.01 and 1.76 μM. Therefore, these experiments indicate that these erlotinib-linked 1,2,3-triazole compounds are potential to act as effective anticancer agents against cervical cancer.

Near-infrared active superparamagnetic iron oxide nanoparticles for magnetomotive optical coherence tomography imaging and magnetic hyperthermia therapeutic applications

A green chemistry-based approach to nanoparticle synthesis is an eco-friendly, simple, and cost-effective way to fabricate nanoparticles. This study aims at the biomedical applications of green synthesized near-infrared (NIR) active superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs obtained by the green synthesis route are non-toxic and their surface is free from any chemical impurity. The MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide] assay was accomplished on human cervical cancer (HeLa) cells and shows that the SPIONs are biocompatible and thus safe for cells even at higher concentrations up to 500 μg/ml. The synthesized SPIONs display an absorbance in the tissue transparent NIR wavelength region. The SPIONs exhibit a superparamagnetic behavior with high saturation magnetization of 66 emu/g. Owing to their excellent optical and magnetic properties, the potential of these green synthesized SPIONs as an exogenous contrast agent in deep-tissue magnetomotive optical coherence tomography (MM-OCT) imaging was evaluated ex-vivo using chicken breast tissue. A significant enhancement in the contrast and the penetration depth was observed with time. The heating response of green synthesized SPIONs was evaluated under the application of an external magnetic field. The results suggest that these SPIONs could be used as theranostic agents for deep tissue biomedical imaging and therapeutic applications.

Proapoptotic activity of essential oils from Syzygium aromaticum, Melaleuca cajuputi, and Cymbopogon nardus on HeLa human cervical cancer cells

Proapoptotic activity of essential oils from Syzygium aromaticum, Melaleuca cajuputi, and Cymbopogon nardus on HeLa human cervical cancer cells

Anticancer Effects of Taraxacum via Cell Cycle Arrest, Necrosis, Apoptosis, and Endoplasmic Reticulum Stress.

Dandelion (Taraxacum species) is a wild plant with over 2500 species. Flavonoids, phenolic compounds, saponins, sesquiterpenes, and sugars have been detected in the organs of Taraxacum, and for centuries it has been used in traditional medicine for the relief and treatment of various diseases. However, details of its working mechanism remain unclear. Bioactive compounds in herbal extracts generally have low yields, which makes their isolation and purification intensive in terms of time and cost. Here, to assess their versatility and safety, we applied aqueous extracts of two species of Taraxacum, T. mongolicum and T. formosanum, including extracts of both fresh and dried T. formosanum, to compare their potential antitumor effects on HeLa human cervical cancer cells, three liver cancer cell lines, and one normal liver cell line. After being treated with a lower dose of Taraxacum, the upregulation of subG1 and S populations, as well as increased levels of p-eIF2[Formula: see text]-to-eIF2[Formula: see text] ratio, were observed in HeLa cells, whereas the downregulation of S population and the absence of mRNA expressions were detected in HeLa cells when being treated with a higher dose of Taraxacum. These results indicated that Taraxacumcould induce apoptosis and endoplasmic reticulum stress while suppressing proliferation, transcription, colony formation, migration, and invasion. What's more, we also found that the effects of fresh T. formosanum were much stronger than that of T. mongolicumin HeLa cells. Based on these results, we suggest that T. formosanum may contain specific compound(s) that are potentially useful for cancer therapy. However, much work remains to identify these effective compounds for the future application of Taraxacumto cancer therapy.

Proliferative Inhibition, Apoptotic Induction, Migratory Suppression of Piper nigrum Extract on HeLa Cervical Cell Line

Piper nigrum is broadly acted as a herbal medicine and anticancer activity as well. Previously, we reported that Piper nigrum extract caused induction of breast cancer cells death and reduction of cell migration in in vitro study. In this present study, we need to explore the anticancer effects of Piper nigrum on the human HeLa cervical cancer cells and underlying mechanism. Sulforhodamine B, colony formation, cell cycle arrest, acridine orange/ethidium bromide staining was performed to analyze cytotoxic effects on the cells. Tetraethylbenzimidazolylcarbocyanine iodide staining, dichlorodihydrofluorescein diacetate staining was used to study apoptotic effects and followed by wound healing method, investigated the cells migration. This Piper nigrum crude extract represented cytotoxic effect against HeLa cervical cancer cells by dose and time-dependent manner with the half-maximal inhibitory concentration values was 48.59±5.37, 36.49±4.34, 22.71±2.12 μg/ml for 24 h, 48 h and 72 h, respectively. Further, these extract caused reduction of cell viability by examining the acridine orange/ethidium bromide staining and decreased the colony formation by dose-dependent manner as well. Next, HeLa cervical cancer cells were significantly arrested in the resting/growth 1 phase and further reported with attenuating mitochondrial function at 24 h incubation, especially at the dose of 100 μg/ml of extract. Then, the molecular mechanisms of Piper nigrum extract were evaluated for reactive oxygen species formation, and data showed that these extracts increased reactive oxygen species production by a dose-dependent amount. On the other hand, the cancer cells migration was suppressed by Piper nigrum extract at 48 h observation time. These results indicated that Piper nigrum extract inhibited HeLa cervical cancer cells through the down-regulation of cell proliferation, induction of apoptosis and attenuation of cell migration. Piper nigrum may be used as anticancer agent for preventing/treating cervical cancer.

Anti-cancer effect of melittin-Au25(MHA)18 complexes on human cervical cancer HeLa cells

Melittin (MEL) is the major component of bee venom, which has recently emerged as an attractive candidate for cancer chemotherapy. As a polypeptide, rapid degradation of MEL is considered as one of the most critical challenges in therapeutic applications. In this study, atomically precise gold nanoclusters with 6-mercaptohexanoic acid (MHA) as a thiolate ligand, termed as Au25(MHA)18, were synthesized and employed as the delivery vehicles of MEL to human cervical cancer HeLa cells. The characterization including Zeta potential, UV–Vis spectra, X-ray photoelectron spectroscopy (XPS), and transmission electron microscope (TEM), showed that Au25(MHA)18 nanoclusters can load MEL with high efficiency, resulting in formation of MEL-Au25(MHA)18 complexes. The anti-cancer effect of MEL-Au25(MHA)18 complexes on human cervical cancer HeLa cells in vitro were further evaluated by cell proliferation and cytotoxicity assay, flow cytometry assay, and confocal microscopy imaging. It was found that Au25(MHA)18 nanoclusters protected MEL from degradation leading to long-lasting cytotoxicity on HeLa cells, and maintained the good anti-cancer activity of MEL. The anti-cancer activity of MEL-Au25(MHA)18 complexes on HeLa cells can be well explained through the pore formation by MEL on the surface of cell membrane, which ultimately leading to cytolysis. This work demonstrated the feasibility of atomically precise gold nanoclusters as the delivery vehicles of unstable polypeptide such as MEL, achieving improved efficiency in chemotherapy.

SYNTHESIS, ANTICANCER ACTIVITIES AND IN SILICO SCREENING OF 3-ACETYLCOUMARINHYDRAZONE SCAFFOLDS

3-acetylcoumarin hydrazone scaffolds, synthesized from 3-acetylcoumarin and substituted benzoic acid hydrazides are reported with structural characterization using IR, HRMS, 1H and 13C-NMR. The In vitro anticancer activities against three human cancer cell lines viz. MCF-7 (human breast cancer cell line), HeLa (human cervical cancer cell line) and SCC-40 (human oral squamous cell carcinoma) are carried out while the tumour selectivity of compounds are tested on the normal human peripheral blood mononuclear cells (PBMCs). The compounds 3ACOH, 3ACDH and 3ACMH exhibited higher sensitivity towards HeLa with GI50 values between 20.4 - 44.1μg/ml and this range of GI50 concentration of hydrazones showed no remarkable toxicity against normal PBMCs. Molecular docking studies revealed commendable binding interactions with cyclooxygenase enzyme (PDB ID 6COX). ADMET analysis shows the hydrazones are showing drug-likeness properties. The reported observations of 3-acetylcoumarin hydrazones suggest their possible role as promising new anticancer drug candidates.

Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells.

The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 was conjugated with mPEG via selenocystamine linkage and then remaining carboxylic acid groups of Ce6 was attached to PBAP (mPEGseseCe6PBAP conjugates). Nanophotosensitizers of mPEGseseCe6PBAP conjugates were prepared by dialysis method. In transmission electron microscope (TEM) observation, nanophotosensitizers of mPEGseseCe6PBAP conjugates have spherical shapes and their diameters were less than 150 nm. The average diameter of mPEGseseCe6PBAP nanophotosensitizers was 92.7 ± 9.6 nm in particle size analysis. When H2O2 was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H2O2 concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H2O2 concentration. When H2O2 was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H2O2 concentration, indicating that nanophotosensitizers showed ROS-sensitive delivery of Ce6 against cancer cells.As well as free Ce6, nanophotosensitizers in the absence of light irradiation have low intrinsic cytotoxicity against RAW264.7 cells and HeLa cells. However, nanophotosensitizers induced cell death dose-dependently under light irradiation. Especially, nanophotosensitizers showed significantly higher ROS generation and phototoxicity against HeLa cells in vitro. When nanophotosensitizers were intravenously administered to animal tumor xenograft model of HeLa cells, tumor tissues revealed stronger fluorescence intensity than other tissues by light irradiation while absence of light irradiation induced relatively lower fluorescence intensity in tumor tissues, indicating that nanophotosensitizers have sensitivity against oxidative stress in tumor tissues. We suggest that nanophotosensitizers of mPEGseseCe6PBAP conjugates are promising vehicle for PDT of cervical cancer cells.

Basic structure and cytocompatibility of giant membrane vesicles derived from paraformaldehyde-exposed human cells.

Exposure of cultured mammalian cells to paraformaldehyde (PFA) is an effective approach to induce membrane blebs, which is followed by their detachment from the cellular cortex to yield giant membrane vesicles in extracellular spaces. Although PFA-induced giant vesicles have attracted significant interest in the field of cell membrane dynamics, their biochemical components and cytocompatibility remain largely unknown. In this report, we exposed human cervical cancer HeLa cells to PFA under metal-free buffer conditions to produce giant vesicles. We analyzed the components and structure of the purified PFA-induced giant vesicles. Co-culturing PFA-induced giant vesicles with exponentially growing HeLa cells resulted in docking of a significant number of the giant vesicles to the cell surface with seemingly no cytotoxicity. Intriguingly, we found that pre-treatment of HeLa cells with peptide-N-glycosidase and neuraminidase was effective in facilitating cellular uptake of constituents residing inside the vesicles. The results revealed further details about the effect of PFA on cell membranes and provide insights for studying the interaction between PFA-induced giant vesicles and cultured cells.