Normal Human Embryonic Kidney Cells Research Articles

Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines.

By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.

Molecular profiling and anti-infective potency of endophytic actinomycetes inhabiting Madhuca insignis Radlk., from Western Ghats of India

BackgroundEndophytic actinomycetes are well known for their diverse bioactive entities and considered as an important source for drug development research. ResultsWe isolated and identified four potential endophytic Streptomyces species, i.e., Streptomyces misionensis MI22, Streptomyces roietensis MI24, Streptomyces glaucescens MI29, and Streptomyces sp. MI04 inhabiting Madhuca insignis by its characteristic morphological features and 16S rRNA gene sequence analysis. S. misionensis MI22 exhibits a broad spectrum of anti-microbial activity against methicillin-resistant Staphylococcus aureus (25.00 ± 1.00 mm) followed by Bacillus subtilis (23.66 ± 0.57 mm), Escherichia coli (22.00 ± 0.00 mm), and Candida albicans (18.00 ± 0.00 mm). Minimum inhibitory concentrations of the ethyl acetate fraction of S. misionensis MI22 against test pathogens were ranged from 25 to 100 μg/mL. Indeed, strain MI22 also exhibited significant anti-proliferative activity against HeLa cell line with IC50 value 98 μg/mL and showed no cytotoxicity effect to the normal human embryonic kidney cell line in the MTT assay. The anti-microbial metabolites from strain MI22 were detected at Rf 0.55 as depicted by the inhibition zone on the intensive band in TLC-bioautography assay. ConclusionThe study indicates that, anti-microbial metabolites of these endophytic Streptomyces species, especially S. misionensis MI22 as a prolific source to discover novel bioactive metabolites to combat multidrug-resistant pathogens.

Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro.

Selenium’s (Se) chemopreventative and therapeutic properties have attracted attention in nanomedicine. Se nanoparticles (SeNPs) retain these properties of Se while possessing lower toxicity and higher bioavailability, potentiating their use in gene delivery. This study aimed to formulate SeNPs for efficient binding and targeted delivery of FLuc-mRNA to hepatocellular carcinoma cells (HepG2) in vitro. The colorectal adenocarcinoma (Caco-2) and normal human embryonic kidney (HEK293) cells that do not have the asialoorosomucoid receptor (ASGPR) were utilized for comparison. SeNPs were functionalized with chitosan (CS), polyethylene glycol (PEG), and lactobionic acid (LA) for ASGPR targeting on HepG2 cells. Nanoparticles (NPs) and their mRNA-nanocomplexes were characterized by Fourier transform infra-red (FTIR) and UV-vis spectroscopy, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Gel and fluorescence-based assays assessed the NP’s ability to bind and protect FLuc-mRNA. Cytotoxicity was determined using the -(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while transgene expression was evaluated using the luciferase reporter gene assay. All NPs appeared spherical with sizes ranging 57.2–130.0 nm and zeta potentials 14.9–31.4 mV. NPs bound, compacted, and protected the mRNA from nuclease digestion and showed negligible cytotoxicity in vitro. Targeted gene expression was highest in the HepG2 cells using the LA targeted NPs. These NPs portend to be efficient nanocarriers of nucleic acids and warrant further investigation.

Preparation of Novel Nickel Oxide@ Glutamic/Thiosemicarbazide Nanoparticles: Implications for Cytotoxic and Anti-cancer Studies in MCF-7 Breast Cancer Cells

The present study, evaluate the anti-cancer properties of nickel oxide nanoparticles functionalized by glutamic acid and conjugated with thiosemicarbazide (NiO@Glu/TSC). First, the NiO@Glu/TSC nanoparticles were prepared using co-condensation reaction. Different techniques were achieved for confirming the synthesized nanoparticles such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS), DLS (dynamic light scattering) and ZP (zeta potential) analysis. Interestingly, the transmission electron microscopy (TEM) and scanning electron microscopy (SEM) results indicated that the structure and size of NiO@Glu/TSC nanoparticles were spherical ranging from 20 to 80 nm. NiO@Glu/TSC nanoparticles revealed significant growth inhibition of MCF-7 (human breast cancer) cells with IC50 values of 298.33 μg/mL, while no significant toxicity was evaluated in HEK293 (normal human embryonic kidney) cells after using in vitro toxicity method. Compared with HEK293 cells, MCF-7 cells elucidated a higher sensitivity to NiO@Glu/TSC nanoparticles. To determine the induction of apoptosis or necrosis, cells were double stained with fluorescein isothiocyanate (FITC)-Annexin V and Propidium Iodide (PI) and assessed by flow cytometry. Moreover, to elucidate the nuclear change through apoptosis, Hoechst 33258 staining was examined to investigate morphological features in the nuclei of MCF-7 cells. The results firmly suggest that NiO@Glu/TSC nanoparticles can be as a potential therapeutic agent for cancer treatment.

Phytochemical constituents of sterol-rich fraction from Allium cepa L. and its cytotoxic effect on human embryonic kidney (HEK293) cells.

The present study investigates the cytotoxic effect of the chemical fractions of Allium cepa (yellow variety) on Human Embryonic Kidney (HEK293) cells. Allium cepa was blended into paste and macerated in distilled water before subjecting to liquid-liquid fractionation, yielding the dichloromethane, ethyl acetate (EtOAc), butanol, and aqueous fractions. Their cytotoxicity on HEK293 cells were evaluated via MTT assay. The cytotoxic fraction (EtOAc) was further evaluated for its oxidative, pro-inflammatory, and apoptotic effects on the cells. The incubation of cells with EtOAc led to depleted level of GSH, SOD, and catalase activities, and elevated levels of malondialdehyde, nitric oxide, and myeloperoxidase as well as apoptotic activities. GC-MS analysis of EtOAc revealed allyl ionone, pentadecanoic acid, and phytol acetate as the predominant fatty acids, while ergost-7-en-3β-ol, campesterol, cycloartenol-3β acetate, sitosterol, and fucosterol as the predominant sterols. These results portray the cytotoxic effect of the EtOAc fraction of A. cepa on HEK293 cells. PRACTICAL APPLICATIONS: There have been increasing concerns in the toxicity and safety of foods. Allium cepa (onions) is among the common globally grown and consumed plant food. This study investigated its cytotoxic effect on normal Human Embryonic Kidney (HEK293) Cells. Although only the ethyl acetate fraction was cytotoxic against the cell line, it, however, portrays a need for caution in its usage.

Mitochondria-Targeting Click-Derived Pyridinyltriazolylmethylquinoxaline-Based Y-Shaped Binuclear Luminescent Ruthenium(II) and Iridium(III) Complexes as Cancer Theranostic Agents.

Due to several negative issues, market available drugs have been gradually losing their importance in the treatment of cancer. With a view to discover suitable drugs capable of diagnosing as well as inhibiting the growth of cancer cells, we have aspired to develop a group of theranostic metal complexes which will be (i) target specific, (ii) cytoselective, thus rendering the normal cell unaffected, (iii) water-soluble, (iv) cancer cell permeable, and (v) luminescent, being beneficial for healing the cancer eternally. Therefore, to reach our goal, we have prepared novel Ru(II)- and Ir(III)-based bimetallic and hetero bimetallic scaffolds using click-derived pyridinyltriazolylmethylquinoxaline ligands followed by metal coordination. Most of the compounds have displayed significant cytoselectivity against colorectal adenocarcinoma (Caco-2) and epithiloid cervical carcinoma (HeLa) cells with respect to normal human embryonic kidney cells (HEK-293) compared to cisplatin [cis-diamminedichloroplatinum(II)] along with excellent binding efficacy with DNA as well as serum albumin. Complex [(η6-p-cymene)(η5-Cp*)RuIIIrIIICl2(K2-N,N-L)](PF6)2 [RuIrL] exhibited the best cytoselectivity against all the human cancer cells and was identified as the most significant cancer theranostic agent in terms of potency, selectivity, and fluorescence quantum yield. Investigation of the localization of complex [Ir2L] and [RuIrL] in the more aggressive colorectal adenocarcinoma cell HT-29 indicates that mitochondria are the key cellular target for destroying cancer cells. Mitochondrial dysfunction and G2/M phase cell cycle arrest in HT-29 cell were found to be involved in the apoptotic cell death pathway induced by the test complexes [Ir2L] and [RuIrL]. These results validate the concept that these types of complexes will be reasonably able to exert great potential for tumor diagnosis as well as therapy in the near future.

Evaluation of Metastasis Suppressor Genes Expression and In Vitro Anti-Cancer Effects of Zinc Oxide Nanoparticles in Human Breast Cancer Cell Lines MCF-7 and T47D.

Background:Metallic nanoparticles are useful materials to be applied in biomedical research. In this study, the possible apoptotic and anti-metastatic activity of Zinc Oxide Nanoparticles (ZnONPs) was assessed in breast cancer cells.Methods:First, in vitro cell viability was investigated by MTT assay in two human breast cancer cells (MCF-7 and T47D) and normal Human Embryonic Kidney (HEK293) cells at 37°C overnight. Apoptosis induced by ZnONPs was evaluated by annexin V/PI staining, cell cycle analysis and caspase assay in cancerous cells. Moreover, quantitative real-time PCR was employed for the detection of two metastasis suppressor genes (KAI-1 and NM23) expression in cancerous cells.Results:Data demonstrated that ZnONPs exert a dose-dependent inhibitory effect on the viability of T47D and MCF-7 cells, while no cytotoxic effect was observed on normal HEK293 cells. The mRNA expression levels of KAI-1 and non-metastatic protein (NM23) genes were up-regulated in ZnONP-exposed cancerous cells. ZnONPs were also found to enhance the apoptosis properties of cells by annexin V/PI staining, and caspase assay in cancerous cells. Furthermore, ZnONPs can increase sub-G1 population as compared to negative control.Conclusion:Our findings showed that ZnONPs induce apoptotic activity and can modulate metastasis by up-regulating of KAI-1 and NM23 gene expression in two breast cancer (MCF-7 and T47D) cells.

Isolation, Characterization and Preliminary Cytotoxic and Antifungal Evaluations of Novel Lancifoliate Isolated from Methanol Extract of Conocarpus lancifolius.

Combretaceae is a large family comprising of 500 species and 20 genera distributed in subtropical and tropical regions of the world. Conocarpus genus is an ornamental tree native to coastal and riverine areas of East Africa and is also planted as an ornamental plant in different areas of Pakistan. This genus has proved medicinal value as a cytotoxic, antibacterial, antiprotozoal, anti-leishmanial, antifungal and antidiabetic agent. The current study was designed to screen the selected pharmacological attributes of sulphur containing novel compound isolated from Conocarpus lancifolius using a series of in vitro and molecular docking models. After collection and authentication of plant material, methanolic extract was prepared from which various secondary metabolites were qualitatively examined. The compound was isolated using open column chromatography and the structure was established with spectroscopic techniques such as UV-visible, infrared spectroscopy, proton nuclear magnetic resonance (1H-NMR), 13C NMR (BB, DEPT-135, 90), twodimensional correlation techniques (HMBC, HSQC) and mass spectrometry (HRMS) respectively. C. lancifolius extract and isolated compound were studied for cytotoxic and antifungal potentials using in vitro Sulforhodamine B (SRB) and disc diffusion methods, respectively. Molecular docking studies were conducted to check the interaction of the isolated compound with major oncogenic proteins. Qualitative phytochemical screening revealed the presence of saponins, steroids, flavonoids, anthraquinones, and cardiac glycosides while alkaloids were absent in C. lancifolius extract. Isolated compound was characterized as lancifoliate, which showed cytotoxic activity towards a variety of cancer cell lines including murine lymphocytic leukemia (P-388, IC50 = 2.65μg/ml), human colon cancer (Col-2, IC50 = 0.84μg/ml), human breast cancer (MCF-7, IC50 = 0.72μg/ml) while no cytotoxic activity was observed towards human lung cancer (Lu-1), rat normal glioma cells (ASK, IC50 = 11.6μg/ml) and human embryonic kidney cells (Kek293, IC50 = 6.74μg/ml) respectively. Minimum Inhibitory Concentration (MIC) of Lancifoliate towards Aspergillus fumigatus, Aspergillus nigar (skin sample), Aspergillus flavus (pleural fluid) and Candida albicans (urine and blood samples) was found to be 54.5, 44.8, 43.5, 22.4 and 20.2μg/ml respectively. Moreover, docking results are in strong agreement with our experimental finding, which has identified lancifoliate to be a more potent antiproliferative agent than previously known compound ellipticine. C. lancifolius extract and lancifoliate possess potent cytotoxic and antifungal properties and thus has potential to be further studied. To the best of our knowledge, this is the first study that highlights isolation, identification and pharmacological activities of lancifoliate from Conocarpus lancifolius.

Porous Carbon Microparticles as Vehicles for the Intracellular Delivery of Molecules.

In this study the application of porous carbon microparticles for the transport of a sparingly soluble material into cells is demonstrated. Carbon offers an intrinsically sustainable platform material that can meet the multiple and complex requirements imposed by applications in biology and medicine. Porous carbon microparticles are attractive as they are easy to handle and manipulate and combine the chemical versatility and biocompatibility of carbon with a high surface area due to their highly porous structure. The uptake of fluorescently labeled microparticles by cancer (HeLa) and normal human embryonic Kidney (HEK 293) cells was monitored by confocal fluorescence microscopy. In this way the influence of particle size, surface functionalization and the presence of transfection agent on cellular uptake were studied. In the presence of transfection agent both large (690 nm) and small microparticles (250 nm) were readily internalized by both cell lines. However, in absence of the transfection agent the uptake was influenced by particle size and surface PEGylation with the smaller nanoparticle size being delivered. The ability of microparticles to deliver a fluorescein dye model cargo was also demonstrated in normal (HEK 293) cell line. Taken together, these results indicate the potential use of these materials as candidates for biological applications.

Near-Infrared Fluorescent pH Responsive Probe for Targeted Photodynamic Cancer Therapy

We developed a pH dependent amino heptamethine cyanine based theranostic probe (I2-IR783-Mpip) that can be activated by near infrared light. I2-IR783-Mpip, in acidic condition, exhibited an intense, broad NIR absorption band (820–950 nm) with high singlet oxygen generation upon exposure to NIR light (~850 nm). Theoretical calculations showed that the protonation of the probe in an acidic environment decreased the molecular orbital energy gaps and increased the intramolecular charge transfer efficiency. I2-IR783-Mpip exhibited good photodynamic efficiency towards liver hepatocellular carcinoma cells under physiological and slightly acidic conditions while normal human embryonic kidney cells remained alive under the same conditions. Detection of intracellular reactive oxygen species (ROS) in cells treated with I2-IR783-Mpip after NIR light exposure confirmed PDT efficiency of the probe in acidic environment. Moreover, I2-IR783-Mpip also demonstrated efficient phototoxicity under deep-seated tumour cell system. We believed this is the first PDT agent that possesses intrinsic tumour binding and selectively eradicate tumour in acidic environment under 850 nm NIR lamp.

“Quinoline Consists of 1H‐1,2,3‐Triazole Hybrids: Design, Synthesis and Anticancer Evaluation”

AbstractA series of novel 8‐bromo‐1H‐1,2,3‐triazol‐4‐yl‐2‐methylquinoline derivatives and their Suzuki coupling products were synthesized via Copper catalyzed azide‐alkyne cycloaddition (CuAAC) strategy followed by microwave assisted Suzuki coupling for the development of new series of anticancer agents. The invitro anticancer activity of the synthesized compounds were screened against human breast cancer (MDA‐MB‐231) and melanoma cell lines (B16F10). Among these, compounds 5 c (Azetidine), 5 e (Nitro benzoate), 5 f (fluorobenzyl)‐1H‐pyrazole), 5 g (Boc piperidine), 6 a (cyclo propyl), 6 c (5‐fluoro‐6‐methoxypyridin‐3‐yl)and 6 d (2‐methoxypyridin‐3‐yl) were showed anticancer activity ranging from 13.44 μM to 38.2 μM. The cellular toxicity of the novel compounds was also evaluated using normal human embryonic kidney (HEK) cell lines.

Microwave-Assisted Synthesis and Anticancer Activity of Triazolyl Thiazolidine Derivatives of Pyrene

In a one pot procedure a series of (R)-2-((2S,3S)-3-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-3,6-dihydro-2H-pyran-2-yl)-3-phenylthiazolidin-4-ones 9a-g and 2-((2R)-2-((2S,3S)-3-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-3,6-dihydro-2H-pyran-2-yl)-4-oxo-3-phenylthiazolidin-5-yl)acetic acids 10a-g was prepared by condensation of (2S,3S)-3-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-3,6-dihydro-2H-pyran-2-carbaldehyde with mercapto acids and primary amines in the presence of ZnCl2 under both microwave irradiation and conventional heating conditions. Characterization of new compounds has been done by means of IR, NMR, MS and elemental analysis. The cytotoxicity was assessed against a panel of four different human tumor cell lines: A549 derived from human alveolar adenocarcinoma epithelial cells (ATCC No. CCL-185), Hela derived from human cervical cancer cells (ATCC No. CCL-2), MDA-MB-231 derived from human breast adenocarcinoma cells (ATCC No. HTB22) and HEK 293 (normal human embryonic kidney cell line) using the MTT assays. Among the tested compounds 9e and 10e showed the most potent activity against MCF-7 breast cancer cell line with IC50 values of 1.91 and 1.95 µM whereas 9b, 10b, 9g and 10g showed promising activity against MDA-MB-231 and Hela cell lines with IC50 values of 5.84, 5.74, 7.89 and 7.65 µM respectively.

MiR-152 inhibits the proliferation and invasion of chordoma cells by targeting HOXC8.

ObjectiveMicroRNAs (miRNAs) are non-coding RNAs that affect the expression of their target genes by binding to the 3′-untranslated region. miR-152 has been identified as a critical modulator in tumorigenesis, but its role in chordoma has not been explored. We therefore investigated the role of miR-152 in regulating chordoma cell behavior, and examined the downstream effectors of miR-152.Materials and methodsWe examined the expression of miR-152 in two human chordoma cell lines and in a normal human embryonic kidney cell line. We also analyzed the relationship between miR-152 and homeobox C8 (HOXC8) by bioinformatics analysis and luciferase reporter assay. We determined the effects of miR-152 and HOXC8 expression on chordoma cell behavior.ResultsmiR-152 expression was downregulated in chordoma compared with normal cells. Meanwhile, miR-152 overexpression inhibited chordoma cell proliferation and invasion. The oncogene HOXC8 was a direct target of miR-152, as shown by luciferase reporter and western blot assays.ConclusionsHOXC8 acted as an effector for the suppressive role of miR-152 in chordoma, thereby providing a potential therapeutic target in patients with chordoma.

Synthesis and In Vitro Anticancer Evaluation of Some Benzimidazolium Salts

A series of benzimidazolium salts having 2‐cyanobenzyl (2–6), 2‐(4‐nitrophenyl)ethyl (7–10), (1,3‐dioxoisoindolin‐2‐yl)butyl (11–17) or N‐methylphthalimide (18–22) substitution were synthesized and characterized by spectroscopic and analytical techniques. The in vitro cytotoxic activity of these salts was tested against human colon cancer (DLD‐1), human breast cancer (MDA‐MB‐231), and normal human noncancerous embryonic kidney (HEK‐293T) cell lines using the MTT assay method. The viability rates of the cells were determined by confocal microscopy. The majority of the newly synthesized compounds, with the exception of compounds 2, 3, 8, 11, 12, and 17, displayed high cytotoxic activity against cancerous cells. In fact, compounds 6 and 7 exhibited better results than the positive control drugs, cisplatin and busulfan, against the MDA‐MB‐231 cells. Therefore, compounds 6 and 7 could be considered as anticancer drug candidates for further development.

In vitro and in silico studies on membrane interactions of diverse Capsicum annuum flower γ-thionin peptides.

Thionins are small, cysteine-rich peptides that play an important role in plant defense, primarily through their interactions with membranes. Eight novel γ-thionin peptides (CanThio1-8) were isolated from the flower of Capsicum annuum. Sequence analysis revealed that the peptides cluster into three groups. A representative peptide from each group (CanThio1, 2, and 3) was used for experimental characterization. Interestingly, peptides were found to possess some cytotoxic activity against normal human embryonic kidney cell line but higher cytotoxicity against cancer cell line MCF-7. CanThio3 peptide was chosen as a representative peptide to study the molecular mechanism of action on membranes. Microsecond timescale atomistic simulations of CanThio3 were performed in the presence of a POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipid bilayer. Simulations revealed that CanThio3 interacts with the bilayer and causes lipid thinning in the vicinity. Nonpolar amino acids specific to the α-core region of CanThio3 along with nonpolar residues in the γ-core region are seen to interact with the lipid tails. The differences in the amino acid sequence of CanThio peptides in these regions explain the variability in cytotoxic activities. In summary, our results demonstrate the membrane-mediated activity of a novel series of γ-thionin peptides from C. annuum.

Protein purification from Arachis hypogaea in one step: stability studies and anticarcinogenic analysis.

The study involved purification of trypsin inhibitor from the seeds of Indian peanuts (Arachis hypogaea), a member of leguminosae family. The inhibitor was purified to homogeneity via three sequential step procedure i.e., salt precipitation to anion-exchange chromatography. The purity and molecular mass was detected using SDS PAGE analysis i.e. ~ 16kDa. The purified inhibitor termed as Peanut Trypsin Inhibitor (PTI) which inhibits trypsin belonging to serpins family. Anti- neoplastic potential on breast cancer cells (MCF-7) and normal Human Embryonic Kidney cells (HEK) was determined using MTT assay. PTI exhibited IC50 value of ~ 18.412µg/mL in HEK cells compared to ~ 9.635µg/mL in MCF-7 cells. The values were quite comparable to curcumin, the standard anticancer drug demonstrating IC50 values of ~ 21.581µg/mL and ~ 7.135µg/mL in HEK and MCF-7 respectively. Therefore, we conclude that PTI may be used as supplement along with the conventional drugs for increased efficacy in the treatment of cancer.

Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model

A series of new pyrazolo-benzothiazole hybrids (7–26) were synthesised and screened for their cytotoxic activity towards several cancer cell lines [colon (HT-29), prostate (PC-3), lung (A549), glioblastoma (U87MG)] and normal human embryonic kidney cell line (Hek-293T). Compounds 8, 9, 13, 14, 18, 19, 23, and 24 displayed significant activity, with compound 14 being particularly potent towards all the tested cancer cell lines with IC50 values in the range 3.17–6.77 μM, even better than reference drug axitinib (4.88–21.7 μM). Compound 14 also showed the strongest growth inhibition in 3D multicellular spheroids of PC-3 and U87MG cells. The mechanism of cellular toxicity in PC-3 cells was found to be cell cycle arrest and apoptosis induction through depolarisation of mitochondrial membrane potential, increased ROS production and subsequent DNA damage. Further, compound 14 displayed significant in vitro (VEGFR-2 inhibition) and in vivo [transgenic zebrafish Tg(flila:EGFP) model] antiangiogenic properties. Overall, these results provide strong evidence that compound 14 could be considered for a lead candidate in anticancer and antiangiogenic drug discovery.

Meticulous Taxifolin Releasing Performance by the Zinc Oxide Nanoparticles: As a Short Road to Drug delivery System for Cancer Therapeutics

Zinc oxide nanoparticles have shown promising therapeutic applications in the field of molecular medicine. Taxifolin is a generous flavanonol, and its antioxidant potential is superior to that of other flavonoid compounds owing to its unique structure. However, its low bioavailability is a prime complication for biomedical applications. In the present study we explored the controlled synthesis of biodegradable polymer coated zinc oxide nanoparticles (ZnO) loaded with taxifolin and evaluation for their loading capacity and drug releasing behavioral properties. The prepared nanomaterials were characterized by using Fourier transform infrared spectroscopy, UV spectroscopy, X-ray diffraction analysis, Dynamic light scattering analysis, zeta potential analyzer and Scanning electron and Transmission electron microscopy. From the scanning electron microscope and DLS analysis it is observed that the size of synthesized zinc oxide nanoparticles ranged between 70 and 80 nm whereas the PEG coated and drug coated particle size were about 80 and 90 nm in diameter respectively. FTIR analysis confirmed that the taxifolin molecules were conjugated with PEG coated zinc oxide nanoparticles. X-ray diffraction pattern confirmed that the zinc oxide nanoparticles exhibited were highly crystalline structure. Taxifolin loaded nanoparticles showed a controlled drug release profile with response to various pH levels. The inhibitory concentrations of synthesized biomaterials were found at 30 µg/ml, 33 µg/ml and 27 µg/ml unloaded, PEG loaded and Taxifolin Loaded ZnO nanoparticles respectively, where as the synthesized materials were did not show any adverse effect on control normal Human Embryonic Kidney Cell (HEK). Furthermore, we found significant synthetic phase arrest at cell cycle analysis in the treated group and following apoptotic cell death were evidenced by AO/EtBr and DAPI fluorescence microscopy analysis. Our findings obviously validate that taxifolin loaded zinc oxide nanoparticles could efficiently deliver the drug of interest, and initiate the apoptotic process in the human breast cancer cells. From this study we can conclude that the taxifolin loaded zinc oxide nanoparticles may have potential applications in the field of anticancer drug development.

SOX21-AS1 is associated with clinical stage and regulates cell proliferation in nephroblastoma.

LncRNA SOX21 antisense RNA 1 (SOX21-AS1) dysregulated in many types of human cancer, and functioned as tumor suppressor or promoter depending on tumor types. However, there was no report about the role of SOX21-AS1 in nephroblastoma. In the present study, we first found that SOX21-AS1 expression was elevated in nephroblastoma tissues and cell lines compared with adjacent normal tissues and normal human embryonic kidney cell line, respectively. Moreover, we observed nephroblastoma patients with large tumor size, advanced National Wilms Tumor Study (NWTS) stage or unfavorable histopathological type, and patients that had higher SOX21-AS1 expression levels than nephroblastoma patients with small tumor size, early NWTS stage or favorable histopathological type. The in vitro studies suggested that knockdown of SOX21-AS1 suppressed nephroblastoma cell proliferation and colony formation, and induced cell-cycle arrest through up-regulating p57 expression. In conclusion, our study suggests that SOX21-AS1 functions as oncogenic lncRNA in nephroblastoma, which may provide a novel insight for nephroblastoma carcinogenesis.

Novel 9-(2-(1-arylethylidene)hydrazinyl)acridine derivatives: Target Topoisomerase 1 and growth inhibition of HeLa cancer cells

A series of 9-(2-(1-arylethylidene)hydrazinyl)acridine and its analogs were designed, synthesized and evaluated for biological activities. Various biochemical assays were performed to determine the free radical scavenging capacity of synthesized compounds (4a–4j). Anticancer activity of these compounds was assessed against two different human cancer cell lines viz cervical cancer cells (HeLa) and liver cancer cells (HepG2) as well as normal human embryonic kidney cell line (HEK 293). Compounds 4b, 4d and 4e showed potential anti-proliferative effects on HeLa cells. Based on results obtained from antioxidant and cytotoxicity studies, 4b, 4d and 4e were further studied in detail for different biological activities. 4b, 4d and 4e reduced the cell growth, inhibited metastatic activity and declined the potential of cell migration in HeLa cell lines. Topoisomerase1 (Top1) treated with compounds 4b, 4d and 4e exhibited inhibition of Top1 and prevented DNA replication. Molecular docking results validate that interaction of compounds 4b, 4d and 4e with Top1-DNA complex, which might be accountable for their inhibitory effects. Further it was concluded that compounds 4b, 4d and 4e arrests the cells at S phase and consequently induces cell death through DNA damage in HeLa cells.