HL-60 Cancer Cell Lines Research Articles

Structure and absolute configuration assignments of ochracines F-L, chamigrane and cadinane sesquiterpenes from the basidiomycete Steccherinum ochraceum HFG119.

Ochracines F–L (1–7), seven previously undescribed chamigrane and cadinane sesquiterpenoids, together with four known chamigranes were isolated from cultures of the wood-decaying fungus Steccherinum ochraceum HFG119. Ochracines F–L were structurally characterized by extensive analysis of HRMS and NMR spectroscopic data. The relative configurations were assigned through a combination of NOE correlations and J-based configuration analysis (JBCA), while the absolute configurations were determined by X-ray single-crystal diffraction, and calculated methods (ECD, [α], 13C NMR). All the new isolates were evaluated for their cytotoxicity against five human cancer cell lines HL-60, SMMC-7721, A549, MCF-7, and SW-480, and inhibitory activity on NO production in RAW 264.7 macrophages.

Anticancer effect of green tea extract (GTE)-Loaded pH-responsive niosome Coated with PEG against different cell lines

Despite its excellent anti-cancer capacity in green tea extract (GTE), its applications are constrained by its low bioavailability solubility and poor bioavailability. This study aimed to design and introduce a new, stable plasma, pH-sensitive niosomal (Nio) formulation of GTE using a thin-film hydration process. Instead of cholesterol, cholesterol hemisuccinate (CHEMS) was added to generate pH-sensitivity properties and, using polyethylene glycol (PEG) (Nio / GTE / PEG / CHEMS), pH-sensitivity and plasma stability properties were integrated simultaneously into one delivery device. GC/MS, UV–vis, DLS, optical microscopy, SEM, and TEM techniques were used for the characterization of formulations. The release of formulations with pH-sensitivity was assessed in vitro in two different buffers (pH 5 and 7.4). In vitro pH-sensitivity cytotoxicity experiment was done on three different MCF-7, HepG2, and HL-60 cancer cell lines and one normal cell line (hGF) to guarantee specificity against cancer cells in the formulation. The GTE’s mass assay with GC shows many anticancer polyphenols are in the sample. The pH-responsive formulation provided positive advantages, including pH-sensitive sustained-release (about 77 percent after 24 h at pH 5) followed Higuchi release kinetics, smooth morphology of the globular surface, high trapping efficiency (81 percent), nanometer diameter (240 nm), and high stability after 3 weeks. Exposure of cancer cells to Nio / GTE / PEG / CHEMS has demonstrated excellent performance against MCF-7, HepG2, and HL-60 cell lines by strong cell internalization and synergistic toxic effect (> 50 percent; compared to free GTE). Interestingly, when treated with the formulations, the viability percentage of the normal cell line (hGF) was higher than the cancer cells, which suggests the higher formulation selectivity against cancer cells. Stable plasma, pH-sensitive niosomes will improve bioavailability and strengthen GTE's cytotoxic effect.

Tetrandrine derivatives IVa-IVd: Structural analysis and their inhibition rate against protein tyrosine kinase, and HL60 & A549 cancer cell lines

Four tetrandrine (TET) derivatives (IVa-IVd) have been synthesized by Suzuki reaction of boronic acid derivatives and 5-bromo-tetrandrine obtained by bromination using tetrandrine as the starting material. The structures are analyzed by 1H NMR, 13C NMR and ESI-MS. The inhibition activities of IVa-IVd against HL60 and A549 cancer cell lines have been investigated by CCK-8 assay. The compounds having significant (P <0.040) inhibition activities are secondarily screened by MTT assay. The inhibitory activities of IVa-IVd against protein tyrosine kinases (PTKs) are tested by ELISA. The results show that IVa, IVb and IVc exhibit significant inhibition activities against the two cancer cell lines. The IVb and IVc show highly significant (P <0.001) inhibition activities against fibroblast growth factor receptor 1 (FGFR1).

Synthesis and Cytotoxic Activity of Novel C-23-Modified Asiatic Acid Derivatives

We selectively oxidized the C-23 hydroxyl group in an asiatic acid (AA) derivative and then, for the first time with AA, modification of the C-23 carboxyl group was conducted to synthesize a series of new AA derivatives. The evaluation of their cytotoxic activities against two human cancer cell lines (SKOV-3 and HCT116) using the MTT assay in vitro revealed a distinctive structure activity relationship (SAR) associated with the intramolecular hydrogen bonding of the amide moiety at C-23. According to the established SAR, the cytotoxic activities of four promising compounds were then evaluated against MCF-7, A549, A2780, HepG2 and HL-60 cancer cell lines. Compound 10 had the best cytotoxic activity among all tested derivatives in the HL-60 cell line, giving IC50 = 0.47 μM, while showing no cytotoxic effect against human normal cells (HUVEC).

Synthesis and biological evaluation of ethacrynic acid derivatives bearing sulfonamides as potent anti-cancer agents

A series of ethacrynic acid (2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid) (EA, Edecrin) containing sulfonamides linked via three types of linkers namely 1,2-ethylenediamine, piperazine and 4-aminopiperidine was synthesized and subsequently evaluated in vitro against HL60 and HCT116 cancer cell lines. All the EA analogs, excluding 6a and 6c, showed anti-proliferative activity with IC50s in the micromolar range (less than 4 uM). Three derivatives 6b, 7b and 7e were selected for their interesting dual activity on HL60 cell line in order to be further evaluated against a panel of cancer cell lines (HCT116, A549, MCF7, PC3, U87-MG and SKOV3) as well as on MRC5 as a normal cell line. These compounds displayed IC50 values in nanomolar range against A549, MCF7, PC3 and HCT116 cell lines, deducing the discovery that piperazine or 4-aminopiperidine is the linker’s best choice to develop EA analogs with highly potent anti-proliferative activities own up to 24 nM. Besides, in terms of selectivity, those linkers are more suitable offering safety ratios of up to 63.8.

English

Cassia grandis L. (Fabaceae), a native tree from Amazon Forest, has been used in folk medicine against worms and intestinal parasites, and to treat stomach and respiratory problems, blood diseases, among others uses. This study aimed to evaluate the antioxidant, cytotoxic, antimicrobial, and schistosomicidal activities of the methanolic extract from C. grandis stem bark (CgME) and to elucidate the chemical profile of its active fractions. The antioxidant activity of C. grandis stem bark methanolic extract (CgME) and its fractions were determined by DPPH radical scavenging assay and by the total phenolics and flavonoid contents. The antimicrobial activity was performed by microdilution. The cytotoxicity against MCF-7 (breast), NCI-H292 (lung), and HL-60 (leukemia) cancer cell lines was evaluated by the MTT method. The schistosomicidal activity was investigated in vitro against adult Schistosoma mansoni couple worms. The phytochemical profile of the active fractions was determined by GC-MS and UPLC-MS. The hexane fraction from the CgME was cytotoxic to NCI-H292 and HL-60 cancer cell lines and both major compounds clionasterol and lupeol acetate, determined by GC-MS, are well known for their cytotoxicity against cancer cells. The ethyl acetate fraction (CgEF) exhibited both antibacterial, against multidrug-resistant S. aureus, and schistosomicidal activities, which could be attributed to the presence of flavonoids, such as catechin derivatives, quercetin, and luteolin in the CgEF. These results agree with the popular uses of C. grandis and should stimulate future research on this species. Key words: Antimicrobial activity, antioxidant, Staphylococcus aureus, clinical isolates, Schistosoma mansoni, cytotoxicity. &nbsp

First Total Synthesis and in Vitro Cytotoxicities of Flavesines G and J.

The first total synthesis of flavesines G and J, natural products exhibiting antiviral activity against hepatitis B virus, is described. A robust, protecting-group-free route starting from commercially available natural product 9-azajulolidine allowed us to obtain the title compounds in a four- and five-step sequence accordingly. Flavesines G and J exhibit micromolar cytotoxicity in A549, MCF-7, HepG2, PANC-1, and HL-60 cancer cell lines.

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.

L-asparaginase production and enhancement by Sarocladium strictum: In vitro evaluation of anti-cancerous properties.

Utilization of l-asparaginase has been one of the effective strategies for the treatment of lymphoblastic leukaemia. Since the currently used bacterial l-asparaginase causes side effects, searching for new enzyme sources has been an active field of research. This study focuses on the characterization of an l-asparaginase-producing fungal strain. Sarocladium strictum was identified as a potent enzyme-producing strain. For the enhancement of enzyme production, we used two-level factorial design and response surface methodology. The optimization of significant factors showed a 1·84-fold increase in enzyme production. The Km and Vmax values of the enzyme were 9·74mmoll-1 and 8·19μmolmin-1 . The toxicity of the produced l-asparaginase was measured on K562 and HL60 cancer cell lines and L6 as normal cells. The IC50 values were calculated as 0·4 and 0·5IUml-1 for K562 and HL60 respectively and no significant effect was observed in L6. BrdU proliferation and caspase-3 activity assay in l-asparaginase treated HL60 and K562 cells indicated that cell proliferation rates and apoptotic cell death were reduced. The cytotoxic properties of the produced fungal enzyme indicated significant growth inhibition in cancer cells while having a little toxic effect on normal cells. The possibility of mass production alongside having suitable cytotoxic and kinetic properties suggest the probable use of the produced l-asparaginase for further researches as a potential chemotherapeutic agent. The lack of significant l-glutaminase activity and promising toxicity properties in S. strictum and the closer evolutionary relativeness of fungi enzymes to human enzymes compared to bacterial enzymes suggest a new source with lower toxicity and anti-cancerous properties, causing less side effect problems.

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.

Anti-proliferative profile of Anacardium occidentale polysaccharide and characterization by AFM

This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The molar mass of isolated CG was in the order of 103–104 g/mol, with small protein traces present. Polymer characterization by NMR identified key signals correlating to galactose, glucose, rhamnose and acid-related groups. Three distinct conformational stages were observed by AFM. The impact of CG on cell morphology and viability with both tumor and non-tumor cell lines was studied by AFM and 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay respectively. Antiproliferative activity was confirmed for HCT116 (colorectal carcinoma), B16F10 (melanoma) and HL60 (promyelocytic leukemia) cancer cell lines. A change in cell morphology was demonstrated as an increased surface roughness for HL60. Considering that a CG does not exhibit cytotoxicity to non-tumor lines, it can be seen that the CG shows selectivity for tumor cells and can be a promising biomaterial for future studies.

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.

Cytotoxic p-Terphenyls from a Marine-Derived Nocardiopsis Species.

Three new p-terphenyl derivatives, nocarterphenyls A-C (1-3), along with three known analogues (4-6) were isolated from the marine-derived actinobacterial strain Nocardiopsis sp. OUCMDZ-4936. Their structures were elucidated on the basis of spectroscopic analysis and a single-crystal X-ray diffraction experiment. Compounds 1 and 2 possess a benzothiazole and benzothiazine moiety, respectively, which are rare in the skeleton of p-terphenyls. Nocarterphenyl A (1) showed potent cytotoxic activity against the HL60 and HCC1954 cancer cell lines with the IC50 values of 0.38 and 0.10 μM among 26 human cancer cell lines.

Monoterpenoid indole alkaloids from the fruits of Melodinus henryi

Four undescribed monoterpenoid indole alkaloids, melodinines X1‒X4 (1‒4), together with fourteen known ones, have been isolated from the fruits of Melodinus henryi. Their structures with absolute configurations were elucidated by extensive spectroscopic methods and ECD calculations. Compound 1 shows a significant cytotoxicity to HL-60 cancer cell line with an IC50 value of 0.8 μM.

Ochracines A-E, chamigrane-related norsesquiterpene derivatives from the basidiomycete Steccherinum ochraceum HFG119

Ochracines A-E, five previously undescribed norsesquiterpenes featured by unusual scaffolds biogenetically related to chamigrane, were isolated from the cultures of Steccherinum ochraceum. Ochracines A (1) and B (2) represent the first examples of norsesquiterpenes with an unprecedented 1,2-6,7-diseco-1,8-cyclochamigrane scaffold. Ochracines C-D (3–5) possess an unusual 1,2-6,7-diseco-chamigrane skeleton. Their structures were elucidated by analysis of spectroscopic data. The absolute configuration of ochracine A (1), and the relative configuration of ochracine B (2) were determined by ECD and/or NMR calculations. The biosynthetic pathways for the norsesquiterpenes were proposed. All isolates were evaluated for their cytotoxicity against the five human cancer cell lines HL-60, SMMC-7721, A549, MCF-7, and SW-480.

Metabolomic Profiling and Cytotoxic Tetrahydrofurofuran Lignans Investigations from Premna odorata Blanco.

Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC–HRESIMS. The identified metabolites (1–34) belonged to different chemical classes, including iridoids, flavones, phenyl ethanoids, and lignans. A phytochemical investigation of P. odorata bark afforded one new tetrahydrofurofuran lignan, 4β-hydroxyasarinin 35, along with fourteen known compounds. The structure of the new compound was confirmed using extensive 1D and 2D NMR, and HRESIMS analyses. A cytotoxic investigation of compounds 35–38 against the HL-60, HT-29, and MCF-7 cancer cell lines, using the MTT assay showed that compound 35 had cytotoxic effects against HL-60 and MCF-7 with IC50 values of 2.7 and 4.2 µg/mL, respectively. A pharmacophore map of compounds 35 showed two hydrogen bond acceptor (HBA) aligning the phenoxy oxygen atoms of benzodioxole moieties, two aromatic ring features vectored on the two phenyl rings, one hydrogen bond donor (HBD) feature aligning the central hydroxyl group and thirteen exclusion spheres which limit the boundaries of sterically inaccessible regions of the target’s active site.

Idarubicin-bromelain combination sensitizes cancer cells to conventional chemotherapy.

Objective(s):The primary cytotoxic effects of anticancer drugs like idarubicin, a chemotherapeutic agent, are not limited to neoplastic cells; they also produce similar effects in normal cells. In this study, we hypothesized that the combination of idarubicin-bromelain could make cancer cells more susceptible to cytotoxicity and genotoxicity.Materials and Methods:To test our hypothesis, the optimal concentrations of idarubicin and bromelain were combined and incubated in the HL-60 cancer cell line and normal human mononuclear leukocytes (PBMC) for 24, 48, and 72 hr. Cytotoxicity and genotoxicity were evaluated by measurement of ATP cell viability test, DNA damage, Caspase-3, Acridine orange/ethidium bromide (AO/EB), and DAPI fluorescent dyes in both cell types.Results:The combination of idarubicin-bromelain significantly reduced cell proliferation in the more potent HL-60 compared to PBMC in all incubation times (P<0.05). DNA damage and Caspase-3 levels (except for 24 hr) were also higher in the HL-60 cell line in comparison with PBMC and were statistically significant (P<0.05). The percentages of apoptotic images obtained by DAPI and AO / EB morphological examination were increased in both cells, depending on the combination dose.Conclusion:Based on these results, it can be concluded that idarubicin combined with bromelain produces more cytotoxic effects in low concentrations in comparison with when it was used per se in the HL-60 cells. Conversely, it was found that this combination in PBMC caused less cytotoxicity and less genotoxicity. Taken together, it can be said that this new combination makes cancer cells more sensitive to conventional therapy.

Phytochemical, in-vitro biological and chemo-preventive profiling of Arisaema jacquemontii Blume tuber extracts

BackgroundArisaema jacquemontii is traditionally used in treatment of different diseases. In this study, phytochemical, in vitro biological and chemo-preventive screening of A. jacquemontii was carried out to explore its pharmacological potential.MethodsThe dried tuber of A. jacquemontii was extracted in 11 organic solvent mixture of different polarity. The extracts were screened for phytochemical assays (phenolics and flavonoids), antioxidants potential (free radical scavenging activity, total antioxidant activity, reducing power), biological activities (antibacterial, antifungal, cytotoxic, antileishmanial, protein kinase inhibition), and chemopreventive activities using different cell lines through standard protocols.ResultsSignificant amount phenolic contents were determined in EtOH and MeOH extracts (210.3 ± 3.05 and 193.2 ± 3.15 μg GAE/mg, respectively). Maximum flavonoid content was determined in MeOH extract (22.4 ± 4.04 μg QE/mg). Noteworthy, DPPH scavenging activity was also recorded for MeOH extract (87.66%) followed by MeOH+EtOAc extract (85.11%). Considerable antioxidant capacity (7.8 ± 0.12 μg AAE/mg) and reducing power (3.1 ± 0.15 μg AAE/mg) was observed in extract of MeOH. The LC50 against brine shrimp and leishmanial parasite was found 9.01 and 12.87 μg/mL for n-Hex and CHCl3 extracts, respectively. The highest zone of inhibition against Streptomyces hyphae formation (12.5 ± 1.77 mm) by n-Hex extract. Growth zone of inhibition 13.8 ± 1.08 mm was recorded for EtOAc and MeOH extracts, respectively against Micrococcus luteus while 10.0 ± 0.11 mm for MeOH extract against Aspergillus flavus. In-vitro cytotoxic assay showed that n-Hex extract had higher cytotoxicity against DU-145 prostate cancer and HL-60 cancer cell lines. NF-kB and MTP potential showed 34.01 and 44.87 μg/mL for n-Hex and CHCl3 extracts, respectively in chemo-preventive potential.ConclusionThe study concludes that Arisaema jacquemontii bears significant phytochemical activity and pharmacological activities, this plant can be further explored for isolation of active component against a number of aliments.

Synthesis of dehydro-α-lapachones, α- and β-lapachones, and screening against cancer cell lines

14 new naphthoquinones were prepared and tested against human cancer cell lines PC-3 (prostate), HCT-116 (colon carcinoma), SNB-19 (glioblastoma), HL-60 (leukemia) and MCF-7 (breast), and a nontumor cell line L929 (murine fibroblasts) to determine cytotoxicity with the MTT assay. 8-OH-β-lapachones (14a, 14c, 14d) presented best results, showing low IC50 values and high selectivity for HCT-116 and HL-60 tumor cells.

Cytotoxic cytochalasans from fungus Xylaria longipes

Five new cytochalasans (1–5) were isolated from the rice fermentation of fungus Xylaria longipes, along with seven known compounds cytochalasin P (6), cytochalasin D (7), zygosporin D (8), 7-O-acetylcytochalasin D (9), cytochalasin C (10), 6,7-dihydro-7-oxo-cytochalasin C (11), and 6,7-dihydro-7-oxo-deacetylcytochalasin C (12). Their structures and absolute configurations were determined by extensive experimental spectroscopic methods as well as ECD calculation and GIAO 13C NMR calculation. The cytotoxicity of obtained compounds (1−12) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Compounds 6–8, 11, and 12 showed cytotoxicity with IC50 value ranging from 4.17–37.18 μM.