Human Lung Adenocarcinoma Cancer Cell Research Articles

Exploration of 1,2,3-triazole linked benzenesulfonamide derivatives as isoform selective inhibitors of human carbonic anhydrase

A novel series of 1,2,3-triazole benzenesulfonamide substituted 1,3-dioxoisoindolin-5-carboxylate (7a-l) inhibitors of human α-carbonic anhydrase (hCA) was designed using a tail approach. The design method relies on the hybridization of a benzenesulfonamide moiety with a tail of 1,3-dioxoisoindoline-5-carboxylate and a zinc-binding group on a 1,2,3-triazole scaffold. Among the synthesized analogues, 2‑iodophenyl (7f, KI of 105.00 nM and SI of 2.98) and 2‑naphthyl (7h, KI of 32.11 nM and SI of 3.48) analogues (over off-target hCA I) and phenyl (7a, KI of 50.13 nM and SI of 2.74) and 2,6‑dimethylphenyl (7d, KI of 50.60 nM and SI of 3.35) analogues (over off-target hCA II) exhibited a remarkable selectivity for tumor isoforms hCA IX and XII, respectively. Meanwhile, analogue 7a displayed a potent inhibitory effect against the tumor-associated isoform hCA IX (KI of 18.29 nM) compared with the reference drug acetazolamide (AAZ, KI of 437.20 nM), and analogue 7h showed higher potency (KI of 9.22 nM) than AAZ (KI of 338.90 nM) against another tumor-associated isoform hCA XII. However, adding the lipophilic large naphthyl tail to the 1,3-dioxoisoindolin-5-carboxylate analogues increased both the hCA inhibitory and selective activities against the target isoform, hCA XII. Additionally, these analogues (7a-l) showed IC50 values against the human lung (A549) adenocarcinoma cancer cell line ranging from 129.71 to 352.26 μM. The results of the molecular docking study suggested that the sulfonamide moiety fits snugly into the hCAs active sites and interacts with the Zn2+ ion. At the same time, the tail extension engages in various hydrophilic and hydrophobic interactions with the nearby amino acids, which affects the potency and selectivity of the hybrids.

In Vitro Antiproliferative Activity of Ptaeroxylon obliquum Leaf Extracts, Fractions and Isolated Compounds on Several Cancer Cell Lines

Several cancers are induced by microbial infections or chronic inflammation. Ptaeroxylon obliquum is traditionally used to treat various infections characterized by inflammation. The in vitro antiproliferative and antioxidant activity of P. obliquum leaf extracts, fractions and isolated compounds were determined. Antiproliferative activity was assessed against normal Vero cells, and several cancerous human cells, including human breast cancer (MCF-7), hepatocarcinoma (HepG2), lung adenocarcinoma (A549) and human cervical cancer cells (HeLa) using a colorimetric tetrazolium bromide assay. Radical scavenging activity was tested using the 2,2-diphenyl-1-instrpicrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Obliquumol, O-methylalloptaeroxylin and a mixture of lupeol and β-amyrin were isolated from the chloroform fraction using silica gel open column chromatography. Acetone extracts were toxic to HepG2 cells with IC50 values from 8 to 200 µg/mL but were less toxic to other cells with selectivity index as high as 14. Aqueous extracts and fractions were non-toxic at concentrations tested against all the cell lines (IC50 > 100 µg/mL). Isolated compounds had IC50 values ranging from 52 to 539 µg/mL and 189 to 247 µg/mL against HepG2 and HeLa cells, respectively. Light microscopy showing changes in HepG2 and HeLa cell morphology supported the cytotoxicity of the acetone extracts. Water extracts scavenged ABTS and DPPH radicals with IC50 values as low as 29.06 µg/mL and 43.4 µg/mL. P. obliquum extracts may be useful as sources of anticancer therapy, as they have selective cytotoxicity against cancer cell lines.

Ubenimex Combined with Pemetrexed Upregulates SOCS1 to Inhibit Lung Adenocarcinoma Progression via the JAK2-STAT3 Signaling Pathway.

To study the effects of ubenimex (UBE) combined with pemetrexed (PEM) on lung adenocarcinoma cell behavior and its molecular mechanism, the tissue samples from lung adenocarcinoma patients who received PEM chemotherapy, those with PEM combined with UBE chemotherapy, and healthy volunteers were retrieved and analyzed. The expression levels of the suppressor of cytokine signaling 1 (SOCS1) in the human lung adenocarcinoma cancer cell lines A549 and PC-9 and tissues were detected by qRT-PCR. MTT assay was performed for cell proliferation. Cell apoptosis was detected by flow cytometry. Cell invasion ability was assessed using the Transwell assay. The expression levels of the JAK2/STAT3 signaling pathway proteins and apoptosis-related proteins were detected by Western blot. The antitumor effect of PEM combined with UBE was tested in nude mice using the tumor formation assay. Our results showed that UBE treatment, alone or combined with PEM, inhibited lung adenocarcinoma cell migration, invasion, and proliferation; promoted apoptosis; significantly increased the G0/G1-phase cell ratio; reduced the S-phase cell ratio; and inhibited the in vivo growth of tumor cells. UBE alone or in combination with PEM also inhibited the JAK2/STAT3 signaling pathway in lung adenocarcinoma cells. In addition, UBE combined with PEM therapy was associated with increased SOCS1 expression in patients' serum and knocking down SOCS1 reversed the antitumor effects of UBE and PEM. Overall, combination therapy with UBE and PEM could inhibit the JAK2-STAT3 signaling pathway by upregulating SOCS1 expression to hinder the progression of lung adenocarcinoma cells.

Novel specific cardiac homing peptides to target failing cardiomyocytes

Heart failure (HF) is one of the most prevalent cardiovascular diseases worldwide with high mortality. Although β-blockers are now the cornerstone of HF treatment, they are ineffective in patients’ subpopulations and may cause several side effects. Thus, the development of novel drug delivery systems directly targeting the myocardium in a tissue-specific manner is a promising approach. Two ligands have been characterized to transduce cardiomyocytes (CMs) in vitro as well as cardiac tissue in vivo: the cardiac targeting peptide (CTP) and the primary cardio myocyte (PCM) peptide. However, very little is known about their uptake mechanisms, targeting efficacies, and intracellular distribution. Characterization and optimization of the CTP and PCM peptides through a structure-activity relationship study. Over 100 variants of CTP and PCM peptides have been engineered and screened. The targeting capacity of peptides was evaluated using flow cytometry on neonatal rat ventricular CMs (NRVC) cultured with 6-carboxyfluorescein conjugated peptides. Other cells lines, including human lung adenocarcinoma (A549) and human liver cancer (HepG2) cells, were used to assess the cardiospecificity of the new peptides. Peptide uptake was also monitored by confocal microscopy imaging in NRVC and adult rat ventricular CMs (ARVC), as well as in the ex vivo model. We have generated specific cardiac homing peptides-1 and 2 (i.e., SCHoP-1 and SCHoP-2) with improved properties and increased ability to target and transduce CMs specifically, compared to the parent CTP and PCM peptides. Flow cytometry assays support that SCHoP-1 and SCHoP-2 significantly increase cardiac targeting in living NRVC by 4-fold over the CTP and PCM peptides. No cellular toxicity was observed. SCHoP-1 and SCHoP-2 target preferentially CMs, over A549 and HepG2 cells. We confirmed that they internalize in NRVC and in ARVC localized in the cytosol. CMs internalization is also increased in ex vivo hearts. SCHoP-1 and SCHoP-2 open the way to explore their potential as a targeting moiety to address a therapeutic agent specifically to failing CMs for the treatment of HF.

Enhancement of Dissolving Capacity and Reducing Gastric Mucosa Irritation by Complex Formation of Resibufogenin with β-Cyclodextrin or 2-Hydroxypropyl-β-cyclodextrin.

Resibufogenin (RBG) is a natural medicinal ingredient with promising cardiac protection and antitumor activity. However, poor solubility and severe gastric mucosa irritation restrict its application in the pharmaceutical field. In this study, the inclusion complex of RBG with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared using the co-evaporation method, and the molar ratio of RBG to CD was determined to be approximately 1:2 by continuous variation plot for both CDs. The formation of inclusion complexes between RBG and each CD (RBG/β-CD and RBG/HP-β-CD) was evaluated by phase solubility study, Fourier transform infrared spectroscopy, and thin-layer chromatography. Powder X-ray diffraction and differential scanning calorimetry confirmed drug amorphization and encapsulation in the molecular cage for both CDs. Moreover, the inclusion complexes’ morphologies were observed using scanning electron microscopy. The dissolution rate of the inclusion complexes was markedly improved compared to that of RBG, and the complexes retained their antitumor activity, as shown in the in vitro cytotoxicity assay on a human lung adenocarcinoma cancer (A549) cell line. Moreover, less gastric mucosal irritation was observed for the inclusion complex. Thus, the inclusion complex should be considered a promising strategy for the delivery of poorly water-soluble anticancer agents, such as RBG.

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.

Phytochemical investigation and cytotoxicity study of Indigofera zollingeriana crude extract

This study aimed to identify the phytochemical constituents in Indigofera zollingeriana (I.zollingeriana) leaves crude extracts and their cytotoxicity activity against different cell lines. The I.zollingeriana leaves were extracted using the cold maceration method, where the leaves were macerated in the ethanol, acetonitrile, acetone, and chloroform separately at room temperature. The total phenolic content (TPC), total tannin content (TTC) and total flavonoid content (TFC) of the crude extract were determined spectrophotometrically. Ethanol extract gave a higher value of TPC, TTC, and TFC (71.38, 50.06, and 8.43 mg/g, respectively) compared to the other solvents. In GC–MS analysis, ethanol extract showed the presence of 59 compounds, while LC-MS analysis showed the abundant presence of triphenylphosphine oxide (95.00%). The cytotoxicity of the ethanol crude extract against different cell lines namely human lung fibroblast (MRC5), African green monkey kidney (Vero), human epithelium lung adenocarcinoma (A549) and human breast cancer (MCF-7) cell lines were determined. The cytotoxicity results revealed that the IC50 for ethanol extract against cancer cells (A549 and MCF-7) were 49.26 and 75.70 µg/ml, respectively. The IC50 value for ethanol extract against Vero cells was 58.98 µg/ml, while for MRC5 cells was declared non-toxic with IC50 value was > 100.00 µg/ml.

Furostanol Saponins from Asparagus cochinchinensis and Their Cytotoxicity

Phytochemical investigation on the roots of Asparagus cochinchinensis led to the isolation of one new furostanol saponin, named 26-O-β-d-glucopyranosyl-22α-hydroxyl-(25R)-Δ5(6)-furost-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 4)]-β-d-glucopyranoside (1), along with three known congeners (2‒4). The structure of new saponin was elucidated via comprehensive inspection of its HRMS and NMR spectral data as well as chemical technology, whereas those of known ones were identified by comparison of their NMR and MS spectral data with those reported in literatures. All isolated saponins were evaluated for their cytotoxic effects on two human liver (MHCC97H) and lung adenocarcinoma (H1299) cancer cells in vitro. Among them, both 1 and 2 showed significant cytotoxicity against above mentioned cell lines. Further studies revealed that these two saponins could significantly inhibit their proliferation of MHCC97H and H1299 cells.Graphic

Synthesis, characterization, biological evaluation and molecular docking of a new quinazolinone-based derivative as a potent dual inhibitor for VEGFR-2 and EGFR tyrosine kinases

An efficient process for the preparation of a new ethyl 2-((3-(4-fluorophenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)thio) acetate (5) was described. The prepared derivative was synthesized using the S-arylation method. Several analytical techniques, such as NMR, Raman and infrared spectroscopy, were used to characterize this compound. The compound was screened for cytotoxic activity against three human cancer cell lines: human cervical cancer (HeLa), human lung adenocarcinoma (A549) and triple negative breast cancer (MDA-MB-231) cells using an MTT assay. It exhibited potent cytotoxic activity against the tested cell lines with IC50 values in the low micromolar range when compared to a standard drug, docetaxel. It also displayed potent inhibitory activity towards VEGFR-2 and EGFR tyrosine kinases, reflecting its potential to act as an effective anti-cancer agent. Communicated by Ramaswamy H. Sarma

Photocatalytic and antibacterial activities of AgNPs from Mesua Ferrea seed

The silver nanoparticles have been successfully prepared with Mesua ferrea seed extract by biological method. Characterizations have been made by XRD, FTIR, UV–Vis-NIR, FESEM with EDAX, DLS and HRTEM. Crystal structure and dislocation density were characterized by X-ray diffractometer and reveal that synthesized AgNPs were FCC structure and the size of AgNPs were 15 nm. Field Emission Scanning Electron Microscopy (FESEM) and High-Resolution Transmission Electron Microscope (HRTEM) characterizations were used to determine the morphology and size of the Ag nanoparticles in the range of 18–30 nm. The functional groups of AgNPs were identifying by FT-IR analysis. The UV–Vis-NIR spectral analysis is used to study optical behaviors like absorption and transmission properties of the AgNPs and optical bandgap of 2.7 eV. The dynamic light scattering (DLS) results confirm a good stabilization of the Ag nanoparticles. The photocatalytic activity of nanoparticles prepared via the biological method exhibited a higher photocatalytic activity compared to powders obtained by the hydrothermal method. The photocatalytic studies were evaluated for AgNPs by the degradation of Congo red under sunlight irradiation. The synthesized silver nanoparticles were tested against gram + Ve (Staphylococcus aureus and Bacillus subtilis) and gram − Ve (Salmonella typhi) bacteria for different concentrations like (10, 20, 30, and 40 μg/mL) and the results were discussed. The antimicrobial activity of AgNPs displayed a better zone of inhibition against selected human pathogens. The present study also investigated the toxicity effect of biogenic AgNPs against human lung adenocarcinoma cancer cells and normal human epithelial cells in vitro, and the inhibitory concentrations were found to be 30 and 40 μg/mL, respectively. We are anticipated a medicinal plant for the biological synthesis of AgNPs with the effective biomedical applications.

Free Radical Scavenging and In vitro Cytotoxic Activity of Bugnay (Antidesma bunius) Leaves Extract against A549 Human Lung Adenocarcinoma and HCT-116 Human Colorectal Cancer Cell Lines

Cancer is one of the significant causes of mortality worldwide. Studies on antineoplastic drugs focused on natural products have revealed several mechanisms to inhibit cancer cells. Bugnay (Antidesma bunius) leaves showed potentials due to its activity observed against brine shrimp and breast cancer cells. However, there is still limited knowledge about its activity against other human cancer cells. This study focused on determining the phytochemical compounds in A. bunius leaves extract, the free radical scavenging activity of the extract using the Diphenylpicrylhydrazyl (DPPH) method, and in vitro cytotoxic activity against two cancer cell lines, namely HCT-116 human colorectal and A549 human lung adenocarcinoma cancer cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The phytochemicals identified were unsaturated lactones, flavonoids, phenolics, diterpenes, saponins, tannins, carbohydrates, and reducing sugars. The extract showed significant free radical scavenging activity and a direct correlation of activity with concentration levels. It also exhibited cytotoxic activity against HCT-116 human colorectal and A549 human lung adenocarcinoma. Hence, A. bunius leaves have the potential to be a source of antioxidant and antineoplastic compounds. This warrant further isolation of the compounds for chemotherapeutic purposes.Keywords: Antidesma bunius, Bugnay, Cancer, Cytotoxicity, Radical

PLCγ1 suppression promotes the adaptation of KRAS-mutant lung adenocarcinomas to hypoxia.

Mutant KRAS modulates the metabolic plasticity of cancer cells conferring growth advantage during hypoxia, but the molecular underpinnings are largely unknown. Using a lipidomic screen, we found that PLCγ1 is suppressed during hypoxia in KRAS-mutant human lung adenocarcinoma cancer cell lines. Suppression of PLCγ1 in hypoxia promotes a less oxidative cancer cell metabolism, reduces the formation of mitochondrial reactive oxygen species and switches tumor bioenergetics towards glycolysis by impairing Ca2+ entry into the mitochondria. This event prevents lipid peroxidation, antagonizes apoptosis and increases cancer cell proliferation. Accordingly, loss-of-function of Plcγ1 in a mouse model of KrasG12D-driven lung adenocarcinoma increased the expression of glycolytic genes, boosted tumor growth and reduced survival. In patients with mutant KRAS lung adenocarcinomas, low PLCγ1 expression correlates with increased expression of hypoxia markers and predicts poor patient survival. Thus, our work reveals a mechanism of cancer cell adaptation to hypoxia with potential therapeutic value.

USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51‐AKT1 signaling

Despite an overall decline in the incidence of new cases, lung adenocarcinoma continues to be a leading cause of cancer death worldwide. Due to lack of gene expression signatures for risk and prognosis stratification of lung adenocarcinoma, identifying novel molecular biomarkers and therapeutic targets may potentially improve lung adenocarcinoma prognosis and treatment. In the current study, we investigate the role of USP53 in lung adenocarcinoma. Bioinformatics analysis, quantitative reverse transcription polymerase chain reaction, and Western blot were employed to examine patterns of gene expression in human lung adenocarcinoma database, patient samples, and cancer cell lines. Stable cell lines were produced by transducing with USP53 overexpression vector or short hairpin RNA targeting USP53 in the presence and absence of AKT pathway inhibitor LY294002. Functional assays were carried out to examine the impact of USP53 and AKT pathway on lung adenocarcinoma cell viability, apoptosis, and glycolysis in vitro, as well as tumor growth in vivo. The correlation between USP53 and FKBP51 was measured by coimmunoprecipitation and ubiquitination assay. Decreased USP53 levels are a reliable marker of lung adenocarcinoma across published datasets, clinical samples, and cell culture lines. Low USP53 expression is linked to decreased apoptosis and increased metabolic activity, suggesting it acts as a tumor suppressor. USP53 regulates cell apoptosis and glycolysis through the AKT1 pathway. Mechanistically, USP53 deubiquitinates FKBP51, which in turn dephosphorylates AKT1, and ultimately inhibits tumor growth in lung adenocarcinoma. Taken together, our study establishes USP53 as a novel regulator of AKT1 pathway with an important role in tumorigenesis in lung adenocarcinoma.

Unexplored features of Ru(ii) polypyridyl complexes - towards combined cytotoxic and antimetastatic activity.

The well-documented cytotoxic activity of coordinatively saturated and substitutionally inert polypyridyl Ru(ii) complexes substantiates their high potency as antiproliferative agents against primary tumors. However, the primary cause of cancer morbidity and mortality responsible for about 90% of cancer deaths is the occurrence of metastasis. Therefore, scientists have to concentrate their efforts on designing compounds affecting not only the primary tumor, but also efficiently inhibiting metastasis. Herein, we report two families of Ru(ii) polypyridyl complexes bearing 2,2'-bipyridine substituted by a semicarbazone 2-formylopyridine moiety as one of the ligands and 4,4'-di-tert-butyl-2,2'-dipyridyl or 4,7-diphenyl-1,10-phenanthroline as auxiliary ligands. These complexes strengthen cells' adherent properties and inhibit the activity of metalloproteinases (MMPs) in vitro, which is relevant in anti-metastatic treatment. The in vitro studies were performed on human lung adenocarcinoma (A549) and human pancreatic cancer (PANC-1) cells, which have a well-documented invasive potential. The induced alteration of the tumor cells' adhesion properties correlated with the high cytotoxic effect exerted by the complexes and their excellent cellular uptake. It was also proved that both complexes directly inhibit M-MP2 and M-MP9 enzyme activities, which are essential for the development of tumor metastasis. The results of this study indicate that the biological properties of polypyridyl Ru(ii) complexes extend beyond the standard cytotoxic activity and represent an important step towards designing new anti-metastatic agents.

MiR-21 improves invasion and migration of drug-resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1.

This study was aimed at the investigation of the effects of miR‐21 on drug resistance, invasion, migration, and epithelial–mesenchymal transition (EMT) of lung adenocarcinoma cells and the related molecular mechanisms. Cell viability of A549 cell line was measured by MTT assay. Wound healing assay and transwell assay were, respectively, employed to examine cell migration and invasion abilities. The cells were transfected with miR‐21 mimic or inhibitor using Lipofectamine 3000. The target relationship between miR‐21 and HBP1 was confirmed by luciferase reporter gene assay. Western blot and qRT‐PCR were used to examine the expression of HBP1 and EMT‐related molecules. Compared with A549 cells, drug resistance of A549/PTX cells and A549/DDP cells were obviously stronger. A549/PTX cells and A549/DDP cells had stronger ability of migration and invasion compared with parental A549 cells. Meanwhile, EMT of A549/PTX and A549/DDP was significantly higher than that of A549 cells. MiR‐21 promoted migration, invasion, and EMT of human lung adenocarcinoma cancer cells. Our experiment also verified the target relationship between miR‐21 and HBP1. MiR‐21 may affect migration and invasion ability of drug‐resistant lung adenocarcinoma cells by targeting HBP1, therefore modulating EMT.

Water Solubility Enhancement of Pyrazolo[3,4-d]pyrimidine Derivatives via Miniaturized Polymer-Drug Microarrays.

A miniaturized assay was optimized to evaluate the enhanced apparent water solubility of pyrazolo[3,4-d]pyrimidine derivatives used extensively as anticancer drug scaffolds. The applied amount of drugs used in the reported strategy ranged from 5 to 10 μg per formulation which were dispensed by an inkjet 2D printer directly into a 96-well plate. The selected polymer/drug formulations with high water solubility demonstrated improved cytotoxicity against a human lung adenocarcinoma cancer cell line (A549) compared to the free drugs. We attribute the enhanced efficacy to the improved apparent-solubility of the drug molecules achieved via this methodology. This novel miniaturized method showed promising results in terms of water solubility improvement of the highly hydrophobic pyrazolo[3,4-d]pyrimidine derivatives, requiring only a few micrograms of each drug per tested polymeric formulation. In addition, the reported experimental evidence may facilitate identification of suitable polymers for combination with drug, leading to investigations on biological properties or mechanisms of action in a single formulation.

Discovery of novel jaspine B analogues as autophagy inducer

A series of 2-alkylaminomethyl jaspine B analogues were synthesized and evaluated for their cytotoxic effects on human lung adenocarcinoma, breast cancer, and prostate cancer cell lines and a mouse melanoma cell line. Most of the compounds exhibited moderate to good activity against the cancer cell lines. Compound 7f showed the best overall cytotoxicity on PC-3 cells (IC50 = 0.85 μM). Further mechanistic studies revealed that compound 7f induced marked changes in PC-3 cell morphology, disrupted the mitochondrial membrane potential, and increased expression of the autophagy proteins beclin-1, LC3, and P62.

An Investigation on Cytotoxicity Effect of Putrescine-Sulphur Analogues on Breast Cancer (Mcf-7), Human Lung Adenocarcinoma (A549) and Colorectal Cancer (Hct-8) Cell Lines

Introduction: Cancer is one of the global health problems that has a detrimental effect to a person's life. However, chemotherapeutic agents success are subject to the side effects due to lack of specificity in the drug delivery system to cancer cells and an increase risk of systemic toxicity to the normal cells. Polyamine transport system (PTS) is one of the potential pathways for transporting anticancer agent into specific cancer cells. This is due to the upregulation of PTS in cancer cells compared to normal cells for the proliferation activity. The aim of this study was to investigate the cytotoxicity effect of putrescine-sulphur analogues type 1 (PSA-1) and type 2 (PSA-2) on human lung adenocarcinoma cells (A549), human colorectal adenocarcinoma cells (HCT-8) and human breast adenocarcinoma cell (MCF-7). Materials and method: The cytotoxicity effect of newly synthesized PSA-1 and PSA-2 were evaluated on selected cancer cells; MCF-7, A549 and HCT-8 cell lines. The halfmaximal inhibitory concentration (IC50) obtained from tetrazolium bromide (MTT) assay was derived from the dose-response graph for all cell lines. Results: PSA-2 elicited cytotoxicity effect, eventhough the IC50 values were not potent with IC50 of 5.4 mM, 5.2 mM and 7.0 mM for MCF-7/48h, A549/48h and HCT-8/48h, respectively. The PSA-1 compound exhibited cytotoxicity effect in all cell lines, however, the compound failed to induce anti-proliferation at the concentration of 3 mM and above. The cytotoxicity of PSA-2 compound against MCF-7 cell lines showed higher potency compared to A549 and HCT-8 cell lines. Conclusion: It was suggested that PSA-2 compound was able to exert cytotoxicity effect against selected cancer cells, in low potency and is deemed for further investigation to increase its effectiveness against specific cancer cells.

Biogenic synthesis and spectroscopic characterization of silver nanoparticles using leaf extract of Indoneesiella echioides: in vitro assessment on antioxidant, antimicrobial and cytotoxicity potential

Natural synthesis of metal nanoparticles is gaining more attention in recent years. This article demonstrates the phytochemical synthesis of silver nanoparticles (AgNPs) by using Indoneesiella echioides (L) leaf extract as a reducing and stabilizing agent. Biosynthesis of AgNPs was monitored by UV–visible spectroscopy which revealed intense surface plasmon resonance bands at 420 nm. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction were employed to identify various functional groups and crystalline nature of AgNPs. High-resolution transmission electron microscopy studies demonstrated that synthesized particles were spherical with average size of ~29 nm. In vitro antioxidant effects were analyzed by 2,2′-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), which exhibited 69 and 71 % of scavenging activity, respectively. The antimicrobial activity of green AgNPs displayed better zone of inhibition against selected human pathogens. The present study also investigated the toxicity effect of biogenic AgNPs against human lung adenocarcinoma cancer cells (A549) and normal human epithelial cells (HBL-100) in vitro, and the inhibitory concentrations (IC50) were found to be 30 and 60 µg/mL, respectively. Herein, we propose a previously unexplored medicinal plant for the biological synthesis of AgNPs with potent biomedical applications.

Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues

The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9-15) were evaluated against human lung adenocarcinoma (A549) and human prostate cancer (PC3) cells. This is the first evaluation of the cytotoxicities of these alkaloids in these cancer cell lines and it revealed that analogue 15 had comparable cytotoxic activity to its natural parent compound, (±)-hanishin (3). This study provides useful information for further structural modification of these alkaloids in order to develop novel antitumor agents.