U937 Cancer Cell Research Articles

Phenanthrene, 9,10-dihydrophenanthrene and bibenzyl enantiomers from Bletilla striata with their antineuroinflammatory and cytotoxic activities

Thirteen undescribed phenanthrene and bibenzyl derivatives, named blestanols A-M, including one pair of biphenanthrene enantiomers, two bis 9,10-dihydrophenanthrene ethers, five pairs of 9,10-dihydrophenanthrene/bibenzyl atropisomers, one racemic 9,10-dihydrophenanthrene/bibenzyl dimer, one 9,10-dihydrophenanthrenebibenzyl ether, two pairs of bibenzyl derivatives, and one stilbene, together with 12 known analogues were isolated from the tubers of Bletilla striata. The structures were elucidated via spectroscopic data analysis. 15 compounds were purified to yield enantiomers (a, b) via chiral-phase HPLC, and their configurations were determined by optical rotation values and the comparison of the experimental and calculated electronic circular dichroism (ECD) curves. Blestanols K-L possessed a cycloheptene moiety, which is rarely observed in bibenzyl derivatives. A putative biosynthetic pathway for the identified components is deduced. Among these compounds, 14 compounds showed inhibition of NO production, with IC50 values ranging from 5.0 to 19.0 μM. Eight compounds displayed selective cytotoxic activities against HCT-116, HepG2, BGC-823, A549 or U251 cancer cell lines, with IC50 values ranging from 1.4 to 8.3 μM. In addition, their structure-activity relationships are discussed briefly.

Design, Synthesis, In Silico Studies and In Vitro Anticancer Activity of 3‐(4‐Methoxyphenyl)azetidine Derivatives

AbstractA series of 3‐(4‐methoxyphenyl)azetidine analogues were synthesized and screened for their in vitro anticancer activity against nine different human cancer cell lines using the cell counting kit‐8 (CCK‐8) assay. The synthesized molecules were characterized by 1H NMR, 13C NMR, LCMS and IR analysis. The toxicity, bioavailability and lipophilicity of all the synthesized compounds were predicted by using osiris and molinspiration model. Molecular docking study revealed that, compound 6‐(3‐(3‐(2‐aminopyridin‐4‐yl)‐4‐methoxyphenyl)azetidin‐1‐yl)picolinonitrile (4 A‐17) and 6‐(3‐(4‐methoxy‐3‐(2‐methoxypyridin‐4‐yl)phenyl)azetidin‐1‐yl)picolinonitrile (4 A‐19) were found to be potential inhibitor of human topoisomerase IIα. The cell viability studies exhibited promising antiproliferative activities of the novel synthesized compounds. 4 A‐17 (EC50 0.03 μM) was found to be more potent than standard Doxorubicin (EC50 0.07 μM) in U251 cancer cell lines. Similarly, 4 A‐19 showed considerable potency against four different cancer cell lines (HepG2, U251, A431, 786‐O) with EC50 values ranging from 0.46 to 2.13 μM. These primary findings supported that molecule 4 A‐17 and 4 A‐19 should be subjected to further studies and lead optimization.

Indole-based alkaloids from Ophiocordyceps xuefengensis

Seven undescribed indole-based alkaloids, xuefengins A–D and xuefenglasins A–C, were isolated from natural Ophiocordyceps xuefengensis, along with six known alkaloids. Their structures were elucidated by comprehensive spectroscopy, with absolute configurations confirmed by comparison with calculated electronic circular dichroism spectra. Eleven of the isolates were tested for cytotoxicity against the U937, NB4, MCF-7, Hep G2, and A549 cancer cell lines. Two compounds exhibited moderate activities, with IC50 values of 2.83–25.68 μM and 1.54–12.16 μM. Further pharmacological studies showed that these two compounds inhibit cell proliferation by inducing apoptosis, and decreasing p38 and caspase-3 levels in A549 cells.

In vitro anticancer evaluation of micelles containing N-(4-(2-((4-methoxybenzyl)amino)ethyl)phenyl)heptanamide, an analogue of fingolimod.

Fingolimod has been evaluated for use as an anticancer agent. However, many steps are required to synthesize fingolimod because of its intricate structure. A fingolimod analogue, N-(4-(2-((4-methoxybenzyl)amino)ethyl)phenyl)heptanamide (MPH), also has anti-cancer effects and is easier to synthesize but is poorly soluble in water. To compensate for its poor water solubility, MPH-loaded polymeric micelles were prepared by thin film hydration method using various polymers and the physicochemical properties of the MPH-loaded micelles such as particle size, drug-loading (DL, %), and encapsulation efficiency (EE, %) were evaluated. A storage stability test was conducted to select the final formulation and the release profile of the MPH-loaded micelles was confirmed by in vitro release assay. MPH-loaded mPEG-b-PLA micelles were selected for further testing based on their stability and physicochemical properties; they were stable for stable for 14days at 4°C and 25°C and for 7days at 37°C. They showed anti-cancer efficacy against both A549 and U87 cancer cells. Encapsulation of MPH in polymeric micelles did not decrease the in vitro cytotoxicity of MPH. The findings of this study lay the groundwork for future formulations that enable the effective and stable delivery of poorly water-soluble agents.

Picoline based fluorescence ‘turn-on’ chemosensor for zinc(II) ion recognition, cell imaging and cytotoxicity study: Synthesis, crystal structure, spectroscopy and DFT

A new picoline based ligand, namely 2-hydroxy-5-methyl-3-[{(6-methylpyridin-2-yl)imino}methyl]benzaldehyde (L) and it’s zinc(II) complex, Zn(L)2 (1) have been synthesized and structurally characterized. The ligand (L) selectively interacts with Zn2+ ion in presence of series of cations in CH3CN-H2O (v/v 1:1) in 1 mM HEPES buffer (pH 7.2). The fluorescence intensity of L is significantly enhanced, and it is increased to 52 times on coordination with Zn(II) ion. The fluorescence intensity value of the L does not show any significant change in the pH range 5 to 9, while the extent of emission phenomenon with Zn(II) ions is observed in the said pH range. The detection limit (0.36 µM) and association constant (log Kapp = 13.25) are evaluated by the fluorescence emission experiment. The probe shows reversibility in addition of dihydrogen phosphate (H2PO4−) ion to the 1. Additionally, the ‘turn-on’ fluorescence probe has sufficient cell permeability and intracellular Zn(II) sensing property as envisaged from the microscopic imaging in HEK293T cells. Both L and ZnL2 (1) are innocuous against PBMC (peripheral blood mononuclear cells) but effective antitumor agents against U-937 cancer cells.

Genome-Wide Comparison of the Target Genes of the Reactive Oxygen Species and Non-Reactive Oxygen Species Constituents of Cold Atmospheric Plasma in Cancer Cells.

Simple SummaryCold atmospheric plasma is being applied to treat cancer by virtue of its preferential anti-proliferative effect on cancer cells over normal cells. This study aimed to systemically determine the distribution of target genes regulated by the reactive oxygen species and non-reactive oxygen species constituents of the plasma. After analyzing genome-wide expression data for a leukemia and a melanoma cancer cell line from a public database followed by experimental approaches, PTGER3 and HSPA6 genes were found regulated by the non-reactive oxygen species and non-reactive nitrogen species constituents of the plasma in the cancer cells. This study could contribute to elucidate the molecular mechanism how each physicochemical constituent of the plasma induces the specific molecular changes in cancer cells.Cold atmospheric plasma (CAP) can induce cancer cell death. The majority of gene regulation studies have been biased towards reactive oxygen species (ROS) among the physicochemical components of CAP. The current study aimed to systemically determine the distribution of target genes regulated by the ROS and non-ROS constituents of CAP. Genome-wide expression data from a public database, which were obtained after treating U937 leukemia and SK-mel-147 melanoma cells with CAP or H2O2, were analyzed, and gene sets regulated by either or both of them were identified. The results showed 252 and 762 genes in H2O2-treated U937 and SK-mel-147 cells, respectively, and 112 and 843 genes in CAP-treated U937 and SK-mel-147 cells, respectively, with expression changes higher than two-fold. Notably, only four and two genes were regulated by H2O2 and CAP in common, respectively, indicating that non-ROS constituents were responsible for the regulation of the majority of CAP-regulated genes. Experiments using ROS and nitrogen oxide synthase (NOS) inhibitors demonstrated the ROS- and reactive nitrogen species (RNS)-independent regulation of PTGER3 and HSPA6 when U937 cancer cells were treated with CAP. Taken together, this study identified CAP-specific genes regulated by constituents other than ROS or RNS and could contribute to the annotation of the target genes of specific constituents in CAP.

Synthesis, structure elucidation and dft study of a new thiazole–pyridine anchored nnn donor and it's cobalt(II) complex: In-vitro antitumor activity against U937 cancer cells, dna binding property and molecular docking study

The reaction between 4-(2-bromoacetyl)benzonitrile and 2-benzoylpyridine thiosemicarbazone produces a tridentate NNN ligand, 4-(2-(2-(phenyl(pyridine-2-yl)methylene)hydrazinyl)thiazole-4-yl)benzonitrile (ppytbH). The ligand constructs an octahedral complex with composition [Co(ppytbH)2](ClO4)2.3(H2O) (1) when reacted with cobalt(II) perchlorate salt in acetonitrile methanol (1:1) solution. The structures of ppytbH and 1 have been established by single X-ray crystallography, spectroscopic (1H NMR, IR, UV-Visible and fluorescence), thermal and electrochemical methods. The chemical reactivity and HOMO–LUMO energy of the compounds have been calculated using Density Functional Theory (DFT). The compounds ppytbH and 1 exhibit potential anticancer activity against U937 human monocytic cells and IC50 values are found 12.76 ± 0.75 and 12.83 ± 1.37 µM, respectively. The fluorescence and molecular docking study interpret the intercalative DNA binding mode with the titled molecules.

Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model

Exosomes (EXOs) are naturally occurring nanosized lipid bilayers that can be efficiently used as a drug delivery system to carry small pharmaceutical, biological molecules and pass major biological barriers such as the blood-brain barrier. It was hypothesized that EXOs derived from human endometrial stem cells (hEnSCs-EXOs) can be utilized as a drug carrier to enhance tumor-targeting drugs, especially for those have low solubility and limited oral bioactivity. In this study, atorvastatin (Ato) loaded EXOs (AtoEXOs) was prepared and characterized for its physical and biological activities in tumor growth suppression of 3 D glioblastoma model. The AtoEXOs were obtained in different methods to maximize drug encapsulation efficacy. The characterization of AtoEXOs was performed for its size, stability, drug release, and in vitro anti-tumor efficacy evaluated comprising inhibition of proliferation, apoptosis induction of tumor cells. Expression of apoptotic genes by Real time PCR, Annexin V/PI, tunnel assay was studied after 72 h exposing U87 cells where encapsulated in matrigel in different concentrations of AtoEXOs (5, 10 μM). The results showed that the prepared AtoEXOs possessed diameter ranging from 30–150 nm, satisfying stability and sustainable Ato release rate. The AtoEXOs was up taken by U87 and generated significant apoptotic effects while this inhibited tumor growth of U87 cells. Altogether, produced AtoEXOs formulation due to its therapeutic efficacy has the potential to be an adaptable approach to treat glioblastoma brain tumors.

Picoline Based Fluorescence ‘Turn-On’ Chemosensor for Zinc(II) Ion Recognition, Cell Imaging and Cytotoxicity Study: Synthesis, Crystal Structure, Spectroscopy and DFT

A new picoline based ligand, namely 2-hydroxy-5-methyl-3-[{(6-methylpyridin-2-yl)imino}methyl]benzaldehyde ( L ) and it’s zinc(II) complex, Zn(L) 2 ( 1 ) have been synthesized and structurally characterized. The ligand ( L ) selectively interacts with Zn 2+ ion in presence of series of cations in CH 3 CN-H 2 O (v/v 1:1) in 1 mM HEPES buffer (pH 7.2). The fluorescence intensity of L is significantly enhanced, and it is increased to 52 times on coordination with Zn(II) ion. The fluorescence intensity value of the L does not show any significant change in the pH range 5 to 9, while the extent of emission phenomenon with Zn(II) ions is observed in the said pH range. The detection limit (0.36 µM) and association constant (log K app = 13.25) are evaluated by the fluorescence emission experiment. The probe shows reversibility in addition of dihydrogen phosphate (H 2 PO 4 – ) ion to the 1 . Additionally, the ‘turn-on’ fluorescence probe has sufficient cell permeability and intracellular Zn(II) sensing property as envisaged from the microscopic imaging in HEK293T cells. Both L and ZnL 2 ( 1) are innocuous against PBMC (peripheral blood mononuclear cells) but effective antitumor agents against U-937 cancer cells.

Total Synthesis of Natural Lembehyne C and Investigation of Its Cytotoxic Properties.

The first Z-stereoselective method for the synthesis of the natural marine alkynol lembehyne C, containing a 1Z,5Z,9Z-triene moiety, in 41% yield was developed using the new Ti-catalyzed cross-coupling of oxygenated and aliphatic 1,2-dienes as the key step. It was found for the first time that lembehyne C exhibits moderate cytotoxicity against Jurkat, K562, U937, and HL60 cancer cells and also efficiently induces apoptosis in Jurkat cells, with the cell death mechanism being activated by the mitochondrial pathway. The lembehyne C inhibition of the cell cycle follows the mitotic catastrophe mechanism.

Synthesis and cytotoxic evaluation of gum arabic surface modified cadmium telluride quantum dots

Water-soluble cadmium telluride (CdTe) quantum dots (QDs) were capped with gum Arabic (GA) is a non-toxic, water-soluble glycoprotein polymer commonly used in the food and pharmaceutical industries. The GA was used to stabilise cadmium telluride quantum dots (GA-QDs) and provides functional groups for other molecules such as nucleic acids, peptides and antibodies to be attached to the QDs for biological and biomedical appli- cations. In this study, the GA was used to cap and stabilise QDs using two different methods. These QDs were characterised using Ultraviolet-visible (UV-vis) and Photoluminescence (PL) spectroscopy, X-powder ray diffraction (XRD), High-resolution transmission electron microscopy, zeta potential and particle size distribu- tions. Cytotoxicity of these QDs was also investigated using four different human cell lines; HeLa, MCF-7, PC-3 and U87 cancer cells. The QDs-MPA was capped with 3-mercaptopropionic acid, QDs-GA2 was stabilized and capped with GA at 60 °C for two hours, and QDs-GA12 was stabilized and capped with GA for twelve hours at room temperature (25 °C) with continuous stirring; These QDs were found to be highly luminescent with PL values of 675 nm, 678 nm and 677 nm respectively. The average polydispersity index (PDI) were 0.36 ± 0.02, 0.27 ± 0.02, 0.35 ± 0.01 for QDs-MPA, QDs-GA2 and QDs-GA12, respectively. The average particles size from HRTEM, XRD and hydrodynamic size showed that the QDs-GA have bigger particles sizes; (56.12 nm ± 1.14), (68.69 nm ± 2.08) and (77.85 nm ± 1.69) for QDs-MPA, QD-GA2 and QD-GA12 respectively. Cytotoxicity studies of these QDs were carried out using WST-1 cell proliferation assay on four different tumour cell line. The results showed that these cells were over 50 per cent viable and the QDs-GA capped had higher cell percentage viability.

Synthesis of new alkynyl containing 9-azabicyclo[4.2.1]nonatrienes from diynes and azepines

New 7-alkynyl-9-azabicyclo[4.2.1]nona-2,4,7-triene-9carboxylates were obtained upon the Co(acac)2(dppe)/Zn/ZnI2catalyzed [6p+2p]-cycloaddition of 1,3-diynes to ethyl/phenyl azepine-1-carboxylates. The structures of the obtained azacyclic compounds were established by 1D and 2D NMR spectroscopy. The compounds prepared were tested for antitumor activities in vitro against Jurkat, K562, U937 and HL60 cancer cell lines.

New 1Z,5Z-diene macrodiolides: Catalytic synthesis, anticancer activity, induction of mitochondrial apoptosis, and effect on the cell cycle.

An original scheme was developed for the synthesis of previously undescribed unsaturated macrodiolides containing a 1Z,5Z-diene moiety in 44-80% yields and with high stereoselectivity (>95%) based on the intermolecular esterification of α,ω-diols with α,ω-alka-nZ,(n+4)Z-dienedicarboxylic acids (1,12-dodeca-4Z,8Z-dienedicarboxylic acid, 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid, 1,18-octadeca-7Z,11Z-dienedicarboxylic acid) catalyzed by hafnium triflate [Hf(OTf)4]. The unsaturated dicarboxylic acids were prepared via homo-cyclomagnesiation of tetrahydropyran ethers of O-containing 1,2-dienes with EtMgBr in the presence of Mg metal and the Cp2TiCl2 catalyst (10mol.%) and the subsequent Jones oxidation of pyran ethers formed after the acid hydrolysis of magnesacyclopentanes. The thus prepared macrodiolides exhibit high cytotoxic activity in vitro against Jurkat, K562, U937, Hek293 and HeLa cancer cell lines. It was found that induction of the programmed cell death in Jurkat cells by macrodiolides corresponds to the mitochondrial apoptosis pathway. Also, it was shown that the prepared macrodiolides efficiently suppress phosphorylation of Akt and p38 kinases and CREB transcription factor in cancer cells.

Novel fusion protein NGR-sIL-24 for targetedly suppressing cancer cell growth via apoptosis.

Pro-apoptotic peptides have attracted much attention as promising anticancer agents due to their high activity. However, poor cellular uptake of the peptides is often associated with limited therapeutic application. Cell-penetrating homing peptides (CPHPs) were found to increase cell internalization as well as anticancer efficacy of the peptide conjugates. In this study, we developed a novel recombinant fusion protein composed of sIL-24 peptide as a pro-apoptotic moiety and asparagine-glycine-arginine (NGR) motif as a CD13-targeting CPHP component. In silico analysis demonstrated that flexible GGGGS linker provided the best structure and stability for our designed fusion protein. Cell adhesion experiments showed a significant binding affinity toward high CD13-expressing cells (U937 and A549) for NGR-sIL-24. Moreover, confocal microscopy revealed that NGR strongly facilitated the binding and cellular uptake of sIL-24 in U937 and A549 cancer cells. NGR-sIL-24 treatment markedly inhibited the growth of U937 and A549 cancer cells in a dose and time-dependent manner, without affecting the normal cell line MRC-5. Flow cytometric analysis and Hoechst 33342 staining exhibited potent apoptosis induction in U937 and A549 cells treated with NGR-sIL-24. Further mechanism elucidation uncovered that apoptotic death promoted by NGR-sIL-24 was attributed to upregulation of BiP/GRP78, Bax/Bcl-2, GADD34, cytochrome c release, and cleavage of caspase-3, suggesting NGR-sIL-24 penetration into cancerous cells and subsequent apoptosis induction, mainly through endoplasmic reticulum (ER) stress-dependent and mitochondria-dependent signaling pathways. Our results indicate that the designed recombinant fusion protein NGR-sIL-24 may serve as a potential targeted therapy agent for cancers with high expression of CD13.

Comparative in vitro Studies of the Topoisomerase I Inhibition and Anticancer Activities of Metallated N‐Confused Porphyrins and Metallated Porphyrins

Using the original approach, a series of metallated N-confused porphyrins and metallated porphyrins have been synthesized and characterized. For all the synthesized porphyrins, in vitro studies of cytotoxic activity against K562, U937, HL-60, Jurkat, A549 and HeLa cancer cell lines, the ability to induce apoptosis and effects on the cell cycle as well as the kinetics of proliferative activity of porphyrins and their respective metallated complexes in real time have been developed. The inhibitory activity of metallated porphyrins against human topoisomerase I and the possible mechanism of inhibition have been carried out by modelling using molecular docking.

Induced apoptosis against U937 cancer cells by Fe(II), Co(III) and Ni(II) complexes with a pyrazine-thiazole ligand: Synthesis, structure and biological evaluation

Complexes of iron(II), cobalt(III) and nickel(II) with 4-(4-methoxyphenyl)-2-(2-(1-(pyrazin-2yl)ethylidene)hydrazinyl)thiazole (PyztH) have been synthesized and characterized by elemental analyses, spectroscopic methods, CV measurements and a DFT study. The crystal and molecular structures were determined by the X-ray diffraction method. The complexes have the compositions [Fe(Pyzt)2]Br2 (1), [Co(Pyzt)2]PF6 (2) and [Ni(Pyzt)(PyztH)]ClO4 (3), with an approximate octahedral environment around the metal centre with NNN donor atoms from the two coordinating ligands. The complexes belong to the triclinic crystal system and crystallize in the space group P-1. Complex 1 is stabilized by strong hydrogen bonds, whereas the stability of complexes 2 and 3 is associated to π–π stacking interactions. The chemical reactivity, frontier orbital picture and energies of the HOMO and LUMO of the complexes have been estimated by a DFT study. The complexes are redox active species and respond with a quasi-reversible redox process. The cytotoxicity of the complexes was tested against U-937 human monocytic cells and shows IC50 values of 132 (for 1), 45 (for 2) and 162 µM (for 3). A LDH release assay indicates that 2 and 3 show apoptosis in the tumour cell. Complex 2 induces apoptosis by disrupting the mitochondrial membrane potential and homeostasis leading to cytotoxicity, as envisaged by PARP cleavage. Complexes 1, 2 and 3 show high binding constants (2.01 × 106 M−1 for 1, 1.18 × 107 M−1 for 2 and 2.90 × 107 M−1 for 3) with CTDNA which attest the groove binding nature of the complexes with DNA. The compounds also exhibit a remarkable zone of inhibition against specific tested bacterial and fungal strains. Based on the results, the cobalt complex (2) shows the best antitumor and antimicrobial activity among the complexes under investigation.

Cobalt(I)-catalyzed [6π+2π]-cycloaddition of allenes to N-carbethoxy(phenoxy)azepines for the synthesis of 9-azabicyclo[4.2.1]nona-2,4-dienes

The [6π+2π]-cycloaddition of allenes to N-carbethoxyazepine or N-carbophenoxyazepine catalyzed by the Co(acac)2(dppe)/Zn/ZnI2 system was performed for the first time and gave previously unknown substituted 9-azabicyclo[4.2.1]nona-2,4-dienes and 16-azatricyclo[9.4.1.02,10]hexadeca-2,12,14-trienes in 75–95% yields. The structures of the resulting azacyclic compounds were reliably proved using NMR spectroscopy and X-ray diffraction analysis. The obtained 9-azabicyclo[4.2.1]nona-2,4-dienes and 16-azatricyclo[9.4.1.02,10]hexadeca-2,12,14-trienes showed high antitumor activities in vitro against Jurkat, K562, U937 and HL60 cancer cell lines.

Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells.

Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the screening of microalgae for potential pharmaceutical applications. Here, we show that monoacylglycerides (MAGs) purified from the marine diatom Skeletonema marinoi have selective cytotoxic activity against the haematological cancer cell line U-937 and colon cancer cell line HCT-116 compared to normal MePR-2B cells. LC-MS analysis of the raw extract revealed that in their natural form, MAGs occur as 2-monoacyl derivatives and include mainly C16 and C20 analogues, but they are converted into the corresponding 1-isomers during purification processes. Pure compounds along with the synthetic 1-monoarachidonoylglycerol tested on HCT-116 and U-937 tumor cell lines induced cell death via apoptosis. The mechanism of action was investigated, and we show that it involves the induction of apoptosis through caspase 3/7 activation. These findings pave the way for the possible use of these molecules as potential anticancer agents or as precursors for the generation of new and more potent and selective compounds against tumor cells.

Apoptosis induction effect of Apocynum venetum polyphenol on human U87 glioma cells via NF-κB pathway.

Aim: Apocynum venetum polyphenol (AVP) was used in in vitro glioma cells culture to prove the growth inhibitory effect of AVP on human U87 glioma cells via NF-κB pathway. Materials & methods: The MTT assay, DAPI morphology, quantitative PCR and western blot experiments were used for determination in vitro. Results & conclusion: AVP can also induce U87 cancer cells apoptosis illustrated by DAPI morphology. AVP could enhance the mRNA and protein expression of IκB-α, TNF-α, TRAIL, caspase-3 and caspase-9 in U87 cancer cells and reduce those of NF-κBp65, cIAP-1, cIAP-2, TGF-β2, CyclinD1, VEGF and IL-8. After ammonium pyrrolidine dithiocarbamate (PDTC) treatment, the NF-κBp65 expression was reduced in U87 cells, and AVP could raise these effects. The results of HPLC indicate that AVP mainly contains six constituents. The growth inhibitory effects of AVP on U87 glioma cells are predominantly from these natural active constituents.

Chemical Composition, Antioxidant and Cytotoxicity Activities of Leaves, Bark, Twigs and Oleo-Resin of Dipterocarpus alatus.

Dipterocarpus alatus (Dipterocarpaceae) is a medicinal plant whose use is well known for the treatment of genito-urinary diseases. However, there is no report of its cytotoxic potential. In this study, the chemical composition, antioxidant and cytotoxic activities of extracts of the leaves, bark, twigs and oleo-resin from D. alatus are investigated. Cytotoxicity was measured by the neutral red (NR) assay against HCT116, SKLU1, SK-MEL2, SiHa and U937 cancer cell lines and antioxidant capacity was evaluated by DPPH, ABTS radical scavenging, and ferric reducing antioxidant power (FRAP) assays. The chemical composition was analyzed by gas chromatography–mass spectrometry (GC-MS). Leaf, bark and twig extracts exhibited stronger antioxidant activity than oleo-resin, with bark extract showing the highest antioxidant activity and the highest total phenolic content. All samples showed more cytotoxic activity against the U937 cell line than HCT116, SKLU1, SK-MEL2 and SiHa cells with oleo-resin being more cytotoxic than melphalan against U937 cells. Chemical composition analysis of oleo-resin by GC-MS showed that the major components were sesquiterpenes, namely α-gurjunene (30.31%), (-)-isoledene (13.69%), alloaromadendrene (3.28%), β-caryophyllene (3.14%), γ-gurjunene (3.14%) and spathulenol (1.11%). The cytotoxic activity of oleo-resin can be attributed to the sesquiterpene content, whereas the cytotoxic and antioxidant activities of leaf, bark and twig extracts correlated to total phenolic content.