Human Lung Carcinoma Cell Line Research Articles

Synthesis, in vitro cytotoxic and apoptotic effects, and molecular docking study of novel adamantane derivatives.

[4-(Adamantane-1-carboxamido)-3-oxo-1-thia-4-azaspiro[4.4]nonan-2-yl]acetic acid (4a) and [4-(adamantane-1-carboxamido)-8-nonsubstituted/substituted-3-oxo-1-thia-4-azas-piro[4.5]decane-2-yl]acetic acid (4b-g) derivatives were synthesized; their structures were verified by elemental analysis, infrared spectroscopy, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and massspectroscopy data; and their in vitro cytotoxicity activities were investigated against human hepatocellular carcinoma, human prostate adenocarcinoma, and human lung carcinoma cell lines (HepG2, PC-3, and A549, respectively), and a mouse fibroblast cell line (NIH/3T3). All compounds, exceptcompound 4e, were found as cytotoxic, especially on A549 cells as compared with the other cells (selectivity index = 2.01-11.6). As a further step, the effects of compounds 4a-c on apoptosis induction were tested and the expression of selected apoptosis genes was analyzed. Among the selected compounds, compound 4a induced apoptosis remarkably. Moreover, computational calculations of the binding of compounds 4a-c to the BIR3 domain of the human inhibitor of apoptosis protein revealed ligand-protein interactions at the atomistic level and emphasized the importance of a hydrophobic moiety on the ligands for better binding.

Lung cancer cell-derived EDA-containing fibronectin induces an inflammatory response from monocytes and promotes metastatic tumor microenvironment.

Tumor-associated macrophages (TAMs) play a pivotal role in facilitating tumor growth and metastasis. This tumor-promoting propensity of TAMs sets in as a result of their complex cross-talk with tumor cells mediated primarily by tumor cell-secreted proteins in the tumor microenvironment. To explore such interactions, we employed an immunoscreening approach involving the immunization of Balb-c mice with model human lung carcinoma cell line, A549. From serological examination combined with mass spectrometric analysis, EDA-containing fibronectin (EDAFN ) was identified as a conspicuous immunogenic protein in A549 cell secretome. We showed that A549 secreted EDAFN engages TLR-4 on THP-1 monocytes to drive the proinflammatory response via NF-κB signaling cascade. Conversely, A549 derived EDAFN potentiates their metastatic capacity by inducing epithelial-mesenchymal transition through its autocrine activity. In conclusion, the study proposes a possible mechanism of cellular cross-talk between lung cancer cells and associated monocytes mediated by lung cancer-derived EDAFN and resulting in the establishment of proinflammatory and metastatic tumor microenvironment.

GC-MS analysis and in vitro Antioxidant, Cytotoxicity study of DCM-ME extract of Dendrophthoe falcata (L.F) Ettingsh leave against human lung carcinoma (A-549) and human Chronic Myelogenous leukemia (k-562) cell Line

GC-MS analysis and in vitro Antioxidant, Cytotoxicity study of DCM-ME extract of Dendrophthoe falcata (L.F) Ettingsh leave against human lung carcinoma (A-549) and human Chronic Myelogenous leukemia (k-562) cell Line

Biocompatibility of magnetic nanoparticles coating with polycations using A549 cells

Fe3O4 nanoparticles were obtained by chemical coprecipitation of iron chloride and sodium hydroxide. The morphology and sizes of the obtained nanoparticles were characterized using laser Doppler velocimetry, transmission electron and atomic force microscopy. Then the nanoparticles were stabilized by three polycations (polyethylenimine (PEI), poly(allylamine hydrochloride) (PAH), poly(diallyldimethylammonium chloride) (PDADMAC)) to increase their biocompatibility. The cytotoxicity of the obtained polymer-stabilized nanoparticles was studied using a human lung carcinoma cell line (A549). The biodistribution of nanoparticles stabilized by polycations in human lung carcinoma cells was analyzed by transmission electron microscopy, and the toxicity of nanomaterials was evaluated using toxicity tests and flow cytometry. As a result, the most biocompatible nanoparticle-biopolymer complex was identified. PAH stabilized magnetic nanoparticles demonstrated the best biocompatibility, and the PEI-magnetic nanoparticle complex was the most toxic.

Tropinone-Derived Alkaloids as Potent Anticancer Agents: Synthesis, Tyrosinase Inhibition, Mechanism of Action, DFT Calculation, and Molecular Docking Studies.

A new series of hybrid compounds with tropinone and thiazole rings in the structure was designed and synthesized as potential anticancer agents. They were tested against human multiple myeloma (RPMI 8226), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), and mouse skin melanoma (B16-F10) cell lines. Toxicity was tested on human normal skin fibroblasts (HSF) and normal colon fibroblasts (CCD-18Co). The growth inhibition mechanism of the most active derivative was analyzed through investigation of its effect on the distribution of cell cycle phases and ability to induce apoptosis and necrosis in RPMI 8226 and A549 cancer cells. The tyrosinase inhibitory potential was assessed, followed by molecular docking studies. Compounds 3a–3h show high anticancer activity against MDA-MB-231 and B16-F10 cell lines with IC50 values of 1.51–3.03 µM. Moreover, the cytotoxic activity of the investigated compounds against HSF and CCD-18Co cells was 8–70 times lower than against the cancer cells or no toxicity was shown in our tests, with derivative 3a being particularly successful. The mechanism of action of compound 3a in RPMI 8226 cell was shown to be through induction of cell death through apoptosis. The derivatives show ability to inhibit the tyrosinase activity with a mixed mechanism of inhibition. The final molecular docking results showed for IC50 distinct correlation with experiment.

Dose-independent genotoxic response in A549 cell line exposed to fungicide Iprodione.

The fungicide Iprodione is widely applied in vegetables and raises concern for human health. The A549 human lung carcinoma cell line is a suitable model for assessing the toxicological effects of drugs. The goal of this work was to evaluate the genotoxicity and oxidative stress in the A549 cell line exposed to sublethal concentrations from 3 to 100µg/mL Iprodione considering LC50 = 243.4µg/mL Iprodione, as determined by the MTT assay. Generalized Linear Mixed Models (GLMM) were performed to determine the association between the responses NDI, MNim and MNib and the explanatory variables. Iprodione and solvent were relativized to the control whereas the concentration was included as numeric variable. ANOVA was used for the comparison of treatments. The coefficients of linear association between the explanatory variables and NDI, and the coefficients of logistic association between explanatory variables and MNim were not significant. However, these coefficients showed significant association with MNib only for Iprodione treatment but not for Iprodione concentration, indicating lack of dose-response relationship. Genotoxicity risk assessment indicated that the increase in Iprodione concentrations increased slightly the probability of belonging to the genotoxic category. ANOVA showed significant differences in MNib, and non-significant differences in NDI and MNim among treatments. The oxidative stress analysis performed at 3, 12, and 25μg/mL Iprodione showed a significant and linear increase in SOD, and a significant and linear decrease in GSH and GST. The Dunnett test was significant for GSH at 12 and SOD at 25μg/mL.

Synthesis and Anti-Proliferative Activity of New Acridinyl and Benzothiazolyl-Based Triazole Glycosides via Click Cycloaddition and Their Tetrazolyl Analogs

Novel acridine and benzothiazole substituted 1,2,3-triazole glycosides were synthesized by using Cu(I)-Catalyzed Azide-Alkyne Cycloaddition (CAAC) known as Click reaction. The reaction of the starting substituted alkyne derivatives with glycopyranosyl azides afforded the corresponding 1,2,3-triazole acetylated N-glycoside products under click reaction conditions. In addition, 1,2,3-triazole glycosides with linking spacers between the sugar moiety, and the triazole ring or between the benzothiazole and the triazole rings as isosteric analogs of the synthesized glycosyl triazoles were also prepared by click cycloaddition. Furthermore, new tetrazolyl glycosides attached to the benzothiazole ring system as analogs of triazole glycosides were synthesized. The desired products were examined against different tumor cells such as the human colon (HCT-116), human lung carcinoma (A549), hepatocellular carcinoma (HepG2) and breast (MCF-7) cancer cell lines utilizing MTT assay. Generally, most of the desired compounds showed excellent activities against all tumor cells. The results also, revealed that the highly active compounds are benzothiazolyl-based triazole glycosides.

CUT&RUN detects distinct DNA footprints of RNA polymerase II near the transcription start sites

CUT&RUN is a powerful tool to study protein-DNA interactions in vivo. DNA fragments cleaved by the targeted micrococcal nuclease identify the footprints of DNA-binding proteins on the chromatin. We performed CUT&RUN on human lung carcinoma cell line A549 maintained in a multi-well cell culture plate to profile RNA polymerase II. Long (> 270 bp) DNA fragments released by CUT&RUN corresponded to the bimodal peak around the transcription start sites, as previously seen with chromatin immunoprecipitation. However, we found that short (< 120 bp) fragments identify a well-defined peak localised at the transcription start sites. This distinct DNA footprint of short fragments, which constituted only about 5% of the total reads, suggests the transient positioning of RNA polymerase II before promoter-proximal pausing, which has not been detected in the physiological settings by standard chromatin immunoprecipitation. We showed that the positioning of the large-size-class DNA footprints around the short-fragment peak was associated with the directionality of transcription, demonstrating the biological significance of distinct CUT&RUN footprints of RNA polymerase II.

Synthesis and biological evaluation of new benzo[d][1,2,3]triazol-1-yl-pyrazole-based dihydro-[1,2,4]triazolo[4,3-a]pyrimidines as potent antidiabetic, anticancer and antioxidant agents

A series of new benzo[d][1,2,3]triazol-1-yl-pyrazole-based dihydro-[1,2,4]triazolo[4,3-a]pyrimidine derivatives 4a-p were synthesized and well characterized by using IR, 1H, 13C NMR and mass spectral data. Finally, the structure of the compound 4l was solved unambiguously by single-crystal X-ray diffraction (SXRD) which confirms all the structures 4a–p. The in vitro α-glucosidase inhibition, anticancer (A549 and MCF-7 cell lines) and antioxidant studies of the title compounds 4a–p were screened. Among all the compounds, 4g, 4h and 4n exhibited significant α-glucosidase inhibition activity with the IC50 values 20.12 ± 0.19 µM, 21.55 ± 0.46 µM and 24.92 ± 0.98 µM. Similarly, the compounds 4h, 4d and 4e showed potent anticancer activity against A549 (human lung carcinoma) cell line with IC50 values 3.64 µM, 4.73 µM and 4.56 µM, respectively, whereas the compounds 4c and 4o displayed potent anticancer activity against human breast cancer (MCF-7) cell line with IC50 values of 2.66 µM and 2.11 µM. In addition, the antioxidant activity revealed that the compounds 4e and 4h exhibited potent antioxidant activity (IC50: 4.25 µM and 5.40 µM). To determine the safety profile of the most active compounds 4c, 4d, 4e, 4g, 4h, 4n and 4o were tested against non-cancer HEK293 cell line (human embryonic kidney 293), results in the lower toxicity of these compounds. New benzo[d][1,2,3]triazol-1-yl-pyrazole-based dihydro-[1,2,4]triazolo[4,3-a]pyrimidines were synthesized. The target compounds were showed significant α-glucosidase inhibition, anticancer and antioxidant activities.

The Therapeutic Effects of an Antimicrobial Peptide Protonectin (IL-12) on A549 Cancer Cell Line

In the study, the impact of protonectin (IL-12) on the bioavailability of human lung carcinoma cell line A549 as well as on HFLF healthy lung fibroblast cells was investigated for 24 h and 48 h. Results demonstrated highest cytotoxicity of protonectin on the A549 cell line at 12 µg/ml and 50 µg/ml, and after 48 h and 24 h cell incubation respectively. No cytotoxicity was observed during the incubation of normal HFLF lung cells with the IL-12 peptide. The peptide did not have any significant impact on the hemolysis of human and cattle red blood cells as well as on the viability of human lymphocytes. The effect of protonectin on gene expression of BMI-1 and CD44 as cancer markers was investigated by the real-time RT-PCR. Results indicated that the effect of the peptide on down-regulation of the BMI-1 gene expression was higher compared to CD44 at 12 µg/ml over 24 h and 48 h. A dose and time-dependent pattern was observed in the production of reactive oxygen species (ROS) in the treated A549 cells. From this study, it can be concluded that protonectin has a significant impact on cancer cells for the down-regulation of gene expression of cancer markers and for the up-regulation of the production of ROS.

Short-Chain Hydroxyl CoA Dehydrogenase Probably is the Central Player in DNA Replication and Glucose Consumption in Human Non-Small Lung Carcinoma Cell Line

: Hydroxyl CoA Dehydrogenase (HADH) is one of the key enzymes in fatty acid β-oxidation. Recently, Hydroxyl CoA Dehydrogenase gene mutation and knockdown were found to be correlated with hyperinsulinemia and central nervous system diseases. As the HADH is one of the critical enzymes in the β-oxidation pathway, the interconnection between HADH and tumorigenicity still is unclear. So, we used Short hairpin RNA (ShRNA) to knock down short-chain hydroxyl CoA dehydrogenase (HADHSC) in human non-small lung carcinoma cell line, H1299, followed by checking cell proliferation, DNA replication, and mRNA level of some the most essential enzymes in glycolysis cycle and Krebs. Cell proliferation was checked by comparing the cell numbers in knockdown and control cells. DNA replication in the H1299 cell line was studied after applying 5-ethynyl 2’-deoxyuridine (EDU) and 4’-6 diamidino-2-phenylindol (DAPI) DNA synthesis Assay. The data revealed a significant decrease in cell proliferation and DNA replication in the cells that the HADHSC was knocked down compared to the control cells. Besides, mRNA levels of the enzymes that needed adenosine triphosphate (ATP) for their activity were decreased abruptly. Furthermore, lactate dehydrogenase (LDHA) mRNA level decreased, and glucose uptake assay showed a tremendous decrease in glucose consumption by H1299 cells with HADHSC knockdown.

In Vitro: Cytotoxicity, Apoptosis and Ameliorative Potential of Lawsonia inermis Extract in Human Lung, Colon and Liver Cancer Cell Line

Cancer has emerged as a major public health issue in developed as well as in developing countries. Plant-derived molecules are widely being used in the treatment of cancer due to their minimum side effects. Lawsonia inermis (Henna) is one of the medicinal plants containing many therapeutic properties. In the present study, bioactive components of L. inermis extract were analyzed by LCMS/MS method and validated. Lawsone (3.5%) is primarily responsible for cytotoxic and anti-cancerous activities. These properties were studied on human lung carcinoma (A549), colorectal cancer (DLD1) and Hepatocellular carcinoma (HepG2) cancer cell lines. The activities were assessed by MTT assay, evaluation of apoptosis by measuring the production of Reactive Oxygen Species (ROS) and mitochondrial membrane potential of the cancer cell lines. Moreover, apoptosis in the respective cancer cell lines was also determined by chromatin condensation and DNA fragmentation using Hoechst 33528 and propidium iodide (PI) staining. The preliminary in vitro result of MTT showed that the henna extract induces cytotoxic properties against A549, DLD1, HepG2 with IC50values 490, 480 and 610 μg/ml respectively (more than 40% growth inhibition). In addition, the extract induced a concentration-dependent rise in ROS production which was 84, 102, and 110% in HepG2, DLD1 AND A549 respectively at 300 μg/ml, whereas at 400 μg/ml concentration it was 86, 102, and 106% in respective cell lines while decreasing mitochondrial membrane potential was more than 20% in the investigated cell lines. The extract also provoked changes associated with apoptosis and the data indicate that the ROS production leads to a diminution in mitochondrial membrane potential and this correlated with the extract cytotoxicity.

Effects of Sclareol Against Small Cell Lung Carcinoma and the Related Mechanism: In Vitro and In Vivo Studies.

This study aimed to investigate the anticancer effects and potential mechanisms of sclareol in a human small cell lung carcinoma (SCLC) cell line. Cell viability was determined by the MTT assay. Cell cycle, apoptosis and caspase activity were evaluated by flow cytometry. Cell cycle and DNA damage related protein expression was determined by western blotting. In vivo evaluation of sclareol was carried out in xenografted tumor mice models. Sclareol significantly reduced cell viability, induced G1 phase arrest and subsequently triggered apoptosis in H1688 cells. In addition, this sclareol-induced growth arrest was associated with DNA damage as indicated by phosphorylation of H2AX, activation of ATR and Chk1. Moreover, in vivo evaluation of sclareol showed that it could inhibit tumor weight and volume in a H1688 xenograft model. Sclareol might be a novel and effective therapeutic agent for the treatment of SCLC patients.

The Role of Epidermal Growth Factor Receptor Signaling Pathway during Bovine Herpesvirus 1 Productive Infection in Cell Culture.

Accumulating studies have shown that the epidermal growth factor receptor (EGFR) signaling pathway plays an essential role in mediating cellular entry of numerous viruses. In this study, we report that bovine herpesvirus 1 (BoHV-1) productive infection in both the human lung carcinoma cell line A549 and bovine kidney (MDBK) cells leads to activation of EGFR, as demonstrated by the increased phosphorylation of EGFR at Tyr1068 (Y1068), which in turn plays important roles in virus infection. A time-of-addition assay supported that virus replication at post-entry stages was affected by the EGFR specific inhibitor Gefitinib. Interestingly, both phospholipase C-γ1 (PLC-γ1) and Akt, canonical downstream effectors of EGFR, were activated following virus infection in A549 cells, while Gefitinib could inhibit the activation of PLC-γ1 but not Akt. In addition, virus titers in A549 cells was inhibited by chemical inhibition of PLC-γ1, but not by the inhibition of Akt. However, the Akt specific inhibitor Ly294002 could significantly reduce the virus titer in MDBK cells. Taken together, our data suggest that PLC-γ1 is stimulated in part through EGFR for efficient replication in A549 cells, whereas Akt can be stimulated by virus infection independent of EGFR, and is not essential for virus productive infection, indicating that Akt modulates BoHV-1 replication in a cell type-dependent manner. This study provides novel insights on how BoHV-1 infection activates EGFR signaling transduction to facilitate virus replication.

Phytochemical Constituents, HPLC-PDA-ESI-MS/MS Profile and Bioactivities of Roots and Rhizomes of Prosopis farcta (Banks &amp; Sol.) J. F. Macbr.

Background:The literature survey revealed that there are no sufficient phytochemical and biological studies on the roots and rhizomes of Prosopis farcta (Banks &amp; Sol.) J. F. Macbr., therefore, the present work is concerned with the phytochemical and biological evaluation of this plant.Methods:The shade-dried roots and rhizomes were powdered together, extracted by 85% ethanol and subjected to phytochemical investigation. Biologically, the antioxidant, antidiabetic, cytotoxic, antiallergic and antimicrobial activities were evaluated.Results:The phytochemical investigation resulted in the isolation of 14 compounds including the fatty acid derivative, threo- methyl 9, 10-dihydroxyoctadecanoate (5), that is isolated for the first time from a natural source, in addition to the identification of 72 compounds by HPLC-PDA-ESIMS/ MS analysis including organic acids and their derivatives, flavonoids, anthraquinones and lignan derivatives. Biologically, threo- methyl 9, 10-dihydroxyoctadecanoate (5) exerted a potent cytotoxic effect against human lung carcinoma (A-549) and human colon carcinoma (HCT-116) cell lines. The total alcoholic extract showed a potent DPPH scavenging activity, a significant decrease in the blood glucose level in alloxan-induced diabetic rats and a mild antibacterial effect against Bacillus subtilis, Staphylococcus aureus (G +ve bacteria) and Escherichia coli (G –ve bacteria).Conclusion:This is the first report on the isolation and identification of threo- methyl 9, 10- dihydroxyoctadecanoate (5) from a natural source, and this novel compound exhibited potent cytotoxic activities against A-549 and HCT-116 cell lines. Moreover, this is the first HPLC-PDA-ESIMS/ MS profiling for this plant.

Synthesis and evaluation of the anticancer activity of bischalcone analogs in human lung carcinoma (A549) cell line

Bischalcone has gained much attention because of its wide range of application in pharmaceutical chemistry. This work aims to evaluate the antiproliferation effects and explore the anticancer mechanism of bischalcone analogs on human lung cancer A549 cells. In this study, we synthesized a series of bischalcone analogs via Aldol condensation reaction; MTT method was used to evaluate the antiproliferation effects; the 2′,7′-dichlorofluorescein fluorescence assay was used to determine the intracellular reactive oxygen species levels; the glutathione reductase-DTNB recycling assay was used to detect the redox imbalance; determination of thiobarbituric acid-reactive substance was used to evaluate the lipid peroxidation; Rhodamine 123 was used to test the mitochondrial membrane potential (MMP); the FITC/PI kit was used to detect the apoptosis; Western blotting was used to detect the expression of Bax and Caspase 3. After treatment with curcumin and bischalcone analogs, compounds 1d and 1g, the more stabilities compounds than curcumin, exhibited much higher potency in A549 cells than curcumin and other bischalcone analogs. Further mechanism of action studies revealed that 1d and 1g exhibited more stronger reactive oxygen species production abilities than curcumin and accompanied by the redox imbalance, lipid peroxidation, the loss of MMP, the activition of Bax and Caspase 3, and ultimately resulted in apoptosis of A549 cell. These data suggest that enhancing the reactive oxygen species generation ability of bischalcone analogs may be a promising strategy for the treatment of human lung cancer.

GC-MS analysis, antimicrobial, antioxidant, antilipoxygenase and cytotoxic activities of Jacaranda mimosifolia methanol leaf extracts and fractions.

Jacaranda mimosifolia trees are grown in frost-free regions globally. The aim of this study was to evaluate the methanol crude extract and various fractions of increasing polarity of J. mimosifolia leaves for bioactive metabolites, as well as antimicrobial, antioxidant and anticancer activities. The anti-inflammatory potential of the various fractions of J. mimosifolia leaf extract was studied via the lipoxygenase (LOX) inhibitory assay. Methanol crude extract (ME), derived fractions extracted with chloroform (CF) and ethyl acetate (EAF), and residual aqueous extract (AE) of dried J. mimosifolia leaves were assayed for polyphenolic compounds, their antioxidant, antimicrobial and lipoxygenase (LOX) inhibitory activities, and anticancer properties. Polyphenolic compounds were determined via HPLC while phytochemicals (total phenolics, flavonoids, tannins and ortho-diphenol contents), antioxidant activities (DPPH, hydrogen peroxideperoxide, hydroxyl and superoxide radical anions) and LOX were measured via spectrophotometry. Methanol extracts and various fractions were evaluated for antibacterial activities against Bacillus subtilis, Klebsiella pneumonia, Pseudomonas aeruginosa and Staphylococcus aureus. Antifungal potential of the fractions was tested against three species: Aspergillus flavus, Aspergillus fumigatus and Fusarium oxysporum. The highest values for total phenolic content (TPC), total flavonoid content (TFC), flavonols, tannins and ortho-diphenols were in the ME, followed by CF > EAF > AE. ME also had the highest antioxidant activity with EC50 values 48±1.3, 45±2.4, 42±1.3 and 46±1.3 μg/mL based on the DPPH, hydrogen peroxide, hydroxyl radical and superoxide radical assays, respectively. TPC and TFC showed a significant, strong and positive correlation with the values for each of these antioxidant activities. ME exhibited anti-inflammatory potential based on its LOX inhibitory activity (IC50 = 1.3 μg/mL). ME also had the maximum antibacterial and antifungal potential, followed by EAF > CF > AE. Furthermore, ME showed the strongest cytotoxic effect (EC50 = 10.7 and 17.3 μg/mL) against human hormone-dependent prostate carcinoma (LnCaP) and human lung carcinoma (LU-1) cell lines, respectively. Bioactive compounds present in leaf methanol extracts of J. mimosifolia were identified using gas chromatography–mass spectrometry (GC–MS). Fifteen compounds were identified including phenolic and alcoholic compounds, as well as fatty acids. Our results suggest that J. mimosifolia leaves are a good source of natural products with antioxidant, anti-inflammatory and anti-cancer properties for potential therapeutic, nutraceutical and functional food applications.

Structure of cyclin-dependent kinase 2 (CDK2) in complex with the specific and potent inhibitor CVT-313.

CVT-313 is a potent CDK2 inhibitor that was identified by screening a purine-analogue library and is currently in preclinical studies. Since this molecule has the potential to be developed as a CDK2 inhibitor for cancer therapy, the potency of CVT-313 to bind and stabilize CDK2 was evaluated, together with its ability to inhibit aberrant cell proliferation. CVT-313 increased the melting temperature of CDK2 by 7°C in thermal stabilization studies, thus indicating its protein-stabilizing effect. CVT-313 inhibited the growth of human lung carcinoma cell line A549 in a dose-dependent manner, with an IC50 of 1.2 µM, which is in line with the reported biochemical potency of 0.5 µM. To support the further chemical modification of CVT-313 and to improve its biochemical and cellular potency, a crystal structure was elucidated in order to understand the molecular interaction of CVT-313 and CDK2. The crystal structure of CDK2 bound to CVT-313 was determined to a resolution of 1.74 Å and clearly demonstrated that CVT-313 binds in the ATP-binding pocket, interacting with Leu83, Asp86 and Asp145 directly, and the binding was further stabilized by a water-mediated interaction with Asn132. Based on the crystal structure, further modifications of CVT-313 are proposed to provide additional interactions with CDK2 in the active site, which may significantly increase the biochemical and cellular potency of CVT-313.

Dendropanax Morbifera Extract-Mediated ZnO Nanoparticles Loaded with Indole-3-Carbinol for Enhancement of Anticancer Efficacy in the A549 Human Lung Carcinoma Cell Line.

Dendropanax morbifera is a versatile plant that has been used as a herbal medicine due to its various useful medicinal effects. To protect its active component from biological stress and increase its drug efficacy as well as drug bioavailability, nanoemulsion was prepared. Dendropanax morbifera zinc oxide nanoparticles (DM-ZnO NPs) were synthesized using the plant extract via the co-precipitation method and loaded with active indole-3-carbinol for nanoemulsion formulation using the ultrasonication process. Field emission transmission electron microscope revealed the flower shape of the Dendropanax morbifera indole-3-carbinol zinc oxide nanoemulsion (DM-ZnO-I3C-NE). In contrast, DM-ZnO NPs showed a spheroid shape that coincides agreeably with field emission electron scanning microscope. The hydrodynamic sizes by dynamic light scattering are about 65 ± 3 nm and 239.6 ± 6 nm and the crystallite sizes from X-ray diffraction are 11.52 nm and 16.07 nm for DM-ZnO NPs and DM-ZnO-I3C-NE, respectively. In vitro analysis revealed the cytotoxicity of DM-ZnO-I3C-NE against a human lung cancer cell line (A549) at 12.5 µg/mL as well as reactive oxygen species (ROS) production. The DM-ZnO-I3C-NE-induced ROS generation level was higher than that of DM-ZnO NPs and free indole-3-carbinol. The synergistic effect of DM-ZnO and indole-3-carbinol indicates DM-ZnO-I3C-NE as a potential candidate for future lung cancer drug and could be scope for functional food.

Mixed Oleic Acid-Erucic Acid Liposomes as a Carrier for Anticancer Drugs

Liposomes are mostly known to be prepared from phospholipids and lipids and have a remarkable capacity to encapsulate both lipophobic and lipophilic molecules. However, there is little research on developing fatty acid liposomes for chemotherapy. We have successfully prepared mixed fatty acid liposomes from two monounsaturated fatty acids, namely oleic acid and erucic acid, which stabilised by DOPEPEG2000. The Critical Vesicular Concentration (CVC) of liposomes was found to be within 0.09 to 0.21 mmol dm-3, with an average particle size of 400 nm. Encapsulation of various anticancer drugs such as folinic acid, methotrexate, doxorubicin, or irinotecan resulted in Encapsulation Efficiency (%EE) of up to 90%. Using a 3-(4, 5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the median Inhibitory Concentration (IC50) values of mixed oleic acid-erucic acid encapsulating hydrophilic drugs was remarkably reduced at the end of 24 hours of incubation with the human lung carcinoma cell line A549. The results suggest that mixed oleic acid-erucic acid liposomes are a potential new approach to further develop as an alternative vehicle of various drugs for cancer treatment.