Human Cancer HeLa Cells Research Articles

Monanchoxymycalin C with anticancer properties, new analogue of crambescidin 800 from the marine sponge Monanchora pulchra

A new pentacyclic guanidine alkaloid, monanchoxymycalin C (1) was isolated from a new collection of marine sponge Monanchora pulchra along with the known monanchoxymycalin A (2). The structure of 1 was elucidated on the basis of spectroscopic data. Monanchoxymycalin C exhibits cytotoxic activity against human cancer HeLa cells at low micromolar concentrations, induces apoptosis-related death of malignant cells and inhibits cancer cell colony formation. In addition, synergistic and additive effects have been observed in combination with cisplatin.

Synthesis and biological evaluation of novel 2-arylvinyl-substituted naphtho[2,3-d]imidazolium halide derivatives as potent antitumor agents

Two series of novel 2-arylvinyl-naphtho[2,3-d]imidazol-3-ium iodide derivatives and 2-arylvinyl-naphtho[2,3-d]imidazol-3-ium bromide derivatives were designed and synthesized by the structural combination of YM155 with stilbenoids. All compounds were tested for anti-proliferative activity against PC-3, A375 and HeLa human cancer cell lines. Two of the compounds were selected for further investigation: 12b, which showed potent cytotoxicity against the three tested cell lines with IC50 values in the range of 0.06–0.21 μM, and 7l, which displayed excellent selectivity for PC-3 cells with an IC50 of only 22 nM. Western blot analysis results indicated that both 12b and 7l suppress the expression of Bcl-2 and Survivin proteins, which helps induce apoptosis. As determined by the percent of Annexin V-FITC-positive apoptotic cells, 12b was not only significantly more effective than 7l at a concentration of 100 nM in PC-3 cells but also induced apoptosis in a dose-dependent manner with more potency than 7l at a concentration of 1000 nM in A375 cells. Therefore, compound 12b was chosen for further in-depth studies investigating the mechanism of apoptosis. The results showed that it could activate caspase-3, hydrolyze PARP, and even inactivate ERK. Moreover, 12b arrested A375 cells at S phase in a time-dependent and dose-dependent manner, while having a visible effect on microtubule dynamics. In addition, (E)-2-(2-(1H-indol-3-yl)vinyl)-1-benzyl-3-(2-methoxyethyl)-4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-3-ium bromide (12b) exhibited significant antitumor activity when evaluated in a subcutaneous solid tumor model. Our study reveals that 2-arylvinyl-substituted naphtho[2,3-d]imidazolium scaffolding is a promising new entity for the development of multi-target anticancer drugs.

Sulfur-containing compounds from the roots of Ferula latisecta and their cytotoxic activities

Five new sulfur-containing compounds, with a new geometry (cis) of the propenyl moiety, and five known compounds were isolated from the roots of Ferula latisecta. The structures of these compounds, were elucidated on the basis of spectroscopic data including 1D and 2D NMR experiments and HRMS. All of the isolated compounds were tested against A2780, A549, HeLa, and HCT116 human cancer cell lines and some of them showed moderate cytotoxic activities.

New iron cyclopentadienyl complexes bearing different phosphane co-ligands: Structural factors vs. cytotoxicity

A new family of piano stool iron-cyclopentadienyl compounds bearing different phosphane co-ligands has been synthesized. All the compounds, with the general structure [Fe(Cp)(CO)(PR3)(L)]n (PR3 = triphenylphosphane, 4-(diphenylphosphino) benzoic acid or tris(4-fluorophenyl)phosphane; when L = I, n = 0; when L = 4-aminobenzonitrile, n = +1) were fully characterized by the usual analytical and spectroscopic techniques. Interestingly, compound [Fe(Cp)(CO)(PPh3)I] 1 crystalizes in the orthorhombic space group P212121 and its crystal packing only contains one enantiomer, while compound [Fe(η5-Cp)(CO)(P(Ph-p-F)3)I] 3 crystalizes in the centrosymmetric space group Pbca presenting an important disorder in the structure, probably due to the presence of the two enatiomers in the crystal packing. All the compounds presented adequate stability in aqueous solution and they were tested against cervical HeLa human cancer cells. The cationic complexes bearing triphenylphosphane (4) or tris(4-fluorophenyl)phosphane (6) were found to be highly cytotoxic, causing cell death by apoptosis. The results point out that the electronic features of the new compounds might be related to their cytotoxic activity.

From Vegetable Waste to New Agents for Potential Health Applications: Antioxidant Properties and Effects of Extracts, Fractions and Pinocembrin from Glycyrrhiza glabra L. Aerial Parts on Viability of Five Human Cancer Cell Lines.

Glycyrrhiza glabra cultivation and harvesting produces substantial quantities of aerial parts as waste. With the aim to prospect an innovative valorization of these byproducts, the aerial parts were harvested in May and October and analyzed for their chemical profile, antioxidant properties, and effects on viability of five cancer cell lines. Pinocembrin was the main constituent. A significant protection of lipid peroxidation was observed with the May total extract (IC50 of 4.2 ± 0.4 μg/mL at 30 min of incubation). The effects on viability of HeLa, MCF-7, MDA-MB-231, Caco-2, and PC3 human cancer cells were investigated. All samples shown a remarkable activity with IC50 values below 25 μg/mL. Samples from plants harvested in May exhibited greater activity than those harvested in October. MCF-7 and HeLa were the most sensitive cells with IC50 in the range 2.73-3.01 and 3.28-5.53 μg/mL, respectively. G. glabra aerial parts represent a good source of valuable products.

Design, synthesis and biological evaluation of 8-substituted-6-hydrazonoindolo[2,1-b]quinazolin-12(6H)-one scaffolds as potential cytotoxic agents: IDO-1 targeting molecular docking studies

Herein, we have reported the synthesis of 18 novel 8-substituted tryptanthrin analogues based on our earlier work. All these tryptanthrin analogues were well characterized by 1H &13C NMR, FT-IR, Mass Spectrometry and Elemental Analysis. All these 8-substituted analogues were screened for their anti-oxidant activity by DPPH radical scavenging assay. Out of all the tested compounds, T11, T12, T17 and T18 showed potent anti-oxidant activity. The anti-cancer activity have been performed by using MTT assay protocol and their results depicts that compounds having the 4-pyridyl or 4-carboxyphenyl substituents at the 8th position of the tryptanthrin framework are found to be the most promising cytotoxic agent against A549, MCF-7 and HeLa human cancer cell lines compared to others as well as with the standard drug cisplatin. Moreover, the comparative molecular docking studies against the three protein receptors IDO1, EGFR and HER2 strongly suggested that IDO1 is the best target protein, which exhibits lowest binding energies of −11.73 and −11.61kcalmol−1 for T11 and T12 scaffolds, respectively towards the in vitro anti-cancer activity.

Synthesis, characterization, biological screening and molecular docking studies of 2-aminonicotinaldehyde (ANA) and its metal complexes

The biological and optical importance of the o-aminoaldehyde family of ligands inspired us to evaluate the coordination properties and biological activities of 2-aminonicotinaldehyde (ANA). Here, we report the synthesis, characterization, biological screening and molecular docking studies of ANA and its metal complexes of Ni(II), Pd(II), Co(II) and Cu(II) using various analytical and spectroscopic techniques. The single crystal X-ray diffraction studies of ANA explain the solid-state assembly and an interesting supramolecular herring bone stacking pattern by classical N–H···O/N intra/inter molecular and non-classical C–H···O/N intermolecular H-bonding. ANA and its metal complexes were screened for in vitro anticancer, antimicrobial and anti-oxidant activities. Anticancer activity was tested against HeLa, MCF-7 and HEK293 human cancer cell lines. The [Ni(ANA)2Cl2] complex showed good activity against HeLa and MCF-7, the [Pd(ANA)2Cl2] and [Cu(ANA)2Cl2] complexes against HeLa, and the [Co(ANA)2Cl2] complex against MCF-7. In antimicrobial screening, the [Co(ANA)2Cl2] and [Cu(ANA)2Cl2] complexes were proved to be potent antibacterial and antifungal agents. The anti-oxidant activity of these complexes was investigated through DPPH radical assay, and it was found that all the complexes have good radical scavenging capability. Molecular docking studies were also carried for all the metal complexes against EGFR as a target protein by using Autodock, and the results strongly correlated with the anticancer activity.

Novel chemotypes targeting tubulin at the colchicine binding site and unbiasing P-glycoprotein

Retrospective validation studies carried out on three benchmark databases containing a small fraction (that is 2.80%) of known tubulin binders permitted us to develop a computational platform very effective in selecting easier manageable subsets showing by far higher percentages of actives (about 25%). These studies relied on the hierarchical application of multilayer in silico screenings employing filters implying molecular shape similarity; a structure-based pharmacophore model and molecular docking campaigns. Building on this validated approach, we performed intensive prospective studies to screen a large chemical collection, including up to 3.7 millions of commercial compounds, to across an unexplored and patent space in the search of novel colchicine binding site inhibitors. Our investigation was successful in identifying a pool of 31 initial hits showing new molecular scaffolds (such as 4,5-dihydro-1H-pyrrolo[3,4-c]pyrazol-6-one and pyrazolo[1,5-a]pyrimidine). This panel of new hits resulted antiproliferative activity in the low μM range towards MCF-7 human breast cancer, HepG2 human liver cancer, HeLa human ovarian cancer and SHSY5Y human glioblastoma cell lines as well as interesting concentration-dependent inhibition of tubulin polymerization assessed through fluorescence polymerization assays. Unlike typical tubulin inhibitors, a satisfactorily low sensitivity towards P-gp was also measured in bi-directional transport studies across MDCKII-MDR1 cells for a selected subset of seven compounds.

Synthesis, antimycobacterial screening and molecular docking studies of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthiazole derivatives

A series of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthiazole derivatives (5a–o) were synthesized and screened for inhibitory activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) strains. Five lead compounds (5e, 5f, 5g, 5h, and 5o) were further confirmed from their dose dependent effect against MTB and Bovine–Calmette–Guerin. The most promising compounds 5f (MIC90: 11.32 µg/mL), 5h (MIC90: 11.59 µg/mL), and 5o (MIC90: 23.64 µg/mL) showed strong antitubercular activity against dormant MTB and BCG as well as almost insignificant cytotoxicity up to 100 µg/mL against HeLa, A549, and PANC-1 human cancer cell lines. Further, the synthesized compounds were found to have potential antibacterial activity against Gram-negative bacteria, Escherichia coli, Pseudomonas flurescence and Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis. Most of the synthesized compounds showed moderate activity against fungal strain Candida albicans. Molecular docking studies of these compounds showed significant interactions with crystal structure of the cytochrome P45014α-sterol demethylase (CYP51) PDB ID: 1E9X. Hydrogen bond interactions with SER261 and VAL395 are important interactions for selective inhibition of designed inhibitors. Compounds 5f, 5h, and 5o showed significant interactions with 1E9X. All the experimental results promote us to consider this series as a starting point for the development of novel, selective and more potent antitubercular agents in the future.

Chemical constituents from roots of Actinidia rufa and their cytotoxicity

To investigate the chemical compounds from the roots of Actinidia rufa, nine compounds were isolated by various column chromatography on silica gel and Sephadex LH-20, and high performance liquid chromatography (HPLC). Their structures were elucidated as 2α, 3β, 19α, 23, 24-pentahydroxyurs-12-en-28-oic acid-28-O-β-D-glucopyranoside (1), 2α, 3α, 19α, 24-tetrahydroxyurs-12-en-28-oic acid-28-O-β-D-glucopyranoside (2), 2α, 3α, 24-trihydroxyurs-12-en-28-oic acid (3), 2α, 3α, 24-trihydroxyolean-12-en-28-oic acid (4), 2α, 3α, 23, 24-tetrahydroxyurs -12-en-28-oic acid (5), 2α, 3β, 23, 24-tetrah-ydroxyurs-12-en-28-oic acid (6), 2α, 3β, 23-trihydroxy-12-en-28-oic acid (7), 2α, 3β, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (8), and 2α, 3α, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (9). Compounds 1 and 2 were isolated from the Actinidia genus for the first time. Compounds 2, 3, and 4 showed cytotoxic activity against human SKVO3 and TPC-1 cancer cell lines with IC₅₀ values ranging from 10.99 to 16.41 μmol•L⁻¹, compounds 3 and 4 have cytotoxic activity against human HeLa cancer cell line with IC₅₀ values of 15.53 and 13.07 μmol•L⁻¹, respectively.

Chemical constituents and biological activities of Dianthus elegans var. elegans

Chemical investigation of the aerial parts of Dianthus elegans var. elegans afforded two previously undescribed saponins, named dianosides M-N (1–2), together with four oleanane-type triterpenoid glycosides (3–6). Their structures were elucidated as 3-O-α-L-arabinofuranosyl-16α-hydroxyolean-12-ene-23α, 28β-dioic acid (1) and 3-O-α-L-arabinofuranosyl-(1 → 3)-β-D-glucopyranosyl 16α-hydroxyolean-12-ene-23α-oic acid, 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glycosyl ester (2) by chemical and extensive spectroscopic methods including IR, 1D, 2D NMR and HRESIMS. Both of the saponins were evaluated for their cytotoxicities against HEK-293, A-549 and HeLa human cancer cells using the MTT method. All compounds showed no substantial cytotoxic activity against tested cell lines. However, dianosides M-N and the n-butanol fraction exhibited considerable haemolysis in human erythrocyte cells. The immunomodulatory properties of dianosides M-N were also evaluated in activated whole blood cells by PMA plus ionomycin. Dianosides M-N increased IL-1β concentration significantly whereas the n-butanol fraction slightly augmented IL-1β secretion. All compounds did not change IL-2 and IFN-γ levels considerably.

Exosomes Transfer Among Different Species Cells and Mediating miRNAs Delivery.

Exosomes, the natural vehicles of intercellular communication, transfer proteins, mRNAs, and microRNAs (miRNAs) and mediate many physiological and pathological processes. It is not clear that whether exosomal miRNAs could regulate gene expression across species, though some studies suggest interactions of exosomal miRNAs between cells. In this report, we have isolated exosomes from rat PC12 cells and assessed their internalization by human cancer Hela cells. The internalized exosomes were located in Hela lysosomes. Human PTEN expression was significantly deregulated due to miR-21 delivered by rat cell exosomes. Our results prove that exosomes could incorporate between cells of different species and could regulate the protein expressions in the recipient cells by delivering the enclosed miRNAs. Thus our study foreshadows a futuristic treatment approach of utilizing miRNA enclosed exosome vehicles sans species concerns in combating various diseases/ regulating abnormal proteins. J. Cell. Biochem. 118: 4267-4274, 2017. © 2017 Wiley Periodicals, Inc.

Gardenifolins A-H, Scalemic Neolignans from Gardenia ternifolia: Chiral Resolution, Configurational Assignment, and Cytotoxic Activities against the HeLa Cancer Cell Line.

From the tropical plant Gardenia ternifolia Schumach. and Thonn. (Rubiaceae), eight stereoisomeric 2,3-dihydrobenzo[b]furan neolignans, named gardenifolins A-H (1a-d and 2a-d), were isolated and fully structurally characterized. Reversed-phase chromatography of a stem bark extract afforded two peaks, viz. mixtures I and II, each one consisting of two diastereomers and their respective enantiomers. They were resolved and stereochemically analyzed by HPLC on a chiral phase coupled to electronic circular dichroism (ECD) spectroscopy, giving single ECD spectra of all eight stereoisomers. The double-bond geometries (E or Z) of the gardenifolins A-H and their relative configurations (cis or trans) at the stereogenic centers C-7 and C-8 in the dihydrofuran ring system were assigned by 1D and 2D NMR methods, in particular, using NOE difference experiments, whereas the absolute configurations of the isolated enantiomers were established by ECD spectroscopy by applying the reversed helicity rule. The individual pure gardenifolin isomers A-H showed the most different cytotoxic effects against the human cancer HeLa cell line, with 1d and 2a displaying the highest activities, with IC50 values of 21.0 and 32.5 μM, respectively. Morphological experiments indicated that gardenifolin D (1d) induces apoptosis of HeLa cells at 25 μM.

Two New Coumarins from the Leaves of Phellodendronamurense.

Two new coumarins, PhellodenolsI (1) and J (2), were isolated from the leaves of Phellodendronamurense. The structures of these compounds were elucidated by extensive spectroscopic analysis. The two new compounds were tested against Hela, AGS, and MGC-803 human cancer cell lines and exhibited cytotoxic activities with IC50 values between 18.71± 5.23 μM and 36.92± 4.72 μM. You can submit your Manuscripts at: https://symbiosisonlinepublishing.com/submitManuscript.php

Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium.

Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity.

Synthesis, characterization, cytotoxic activity of half-sandwich rhodium(III), and iridium(III) complexes with curcuminoids

A series of organometallic rhodium and iridium complexes with curcuminoid ligands (1–14) have been synthesized and characterized by NMR, IR, elemental analysis, and HR-ESI-mass spectrometry. The molecular structure of complex 9 has been characterized by X-ray crystallography. The in vitro activity of all the compounds has been evaluated against the HepG2, HeLa human cancer cell lines and HEK-293T human healthy cell lines. The rhodium complex 6 exhibits excellent anticancer activity and promising selectivity towards cancer cell lines. Furthermore, the interaction of 6 with DNA has been followed by electrophoretic mobility spectrometry studies.

In vitro Antioxidant and Cytotoxic Effects of Methanol Extracts of Vitex negundo, Lantana camara, Bauhinia variegata and Barringtonia racemosa on Human Cancer Cell lines

In current study, the phytochemical, antioxidant and cytotoxic effects of methanol extracts of Vitex negundo, Lantana camara, Bauhinia variegata and Bauhinia racemosa were reported. Methanol extract of medicinal plants (V. negundo, L. camara, B. variegata and B. racemosa) were extracted using different extraction methods and then tested for their antioxidant activity by 2,2-diphenylpicrylhydrazyl, superoxide scavenging method, chelation of metal ions and cytotoxic potency using MTT assay on human cancer cell lines. In different extraction methods, highest yield was obtained with hot extraction method. Total phenolic and flavonoid contents were found higher in methanol extract of V. negundo having 173.3±1.54 mg gallic acid equivalent/g DW and 24.41±1.5 mg quercetin equivalent/g DW contents, respectively. Leaves of V. negundo have maximum IC50 value of 73±2.76 µg/ml and 350±1.23 µg/ml in 2,2-diphenylpicrylhydrazyl and iron chelating activity compared to all other methanol extracts. B. racemosa leaves have higher superoxide scavenging effect with IC50 value of 223±1.23 µg/ml. V. negundo and L. camara leaves showed pronounced cytotoxic effect against HELA and KB human cancer cell lines with LD50 value of 222±3.35 and 188.69±1.4 µg/ml, respectively. The present study shows that V. negundo and L. camara may be a probable source of natural antioxidant and as an anticancer drugs.

Cytotoxic activity screening of some Turkish marine sponge species

Marine organisms have proved to be a source of potent pharmacologically active compounds. More than 15.000 marine products have been isolated and tested during the last 23 years, until 2015. Sponges have been a big source of secondary metabolites with a great diversity of structures and bioactivities. Research studies on these sources have resulted in the identification of various bioactive compounds which were tested for their potential antiinflammatory, antimalarial, antitumour, antiviral, antibiotic, antifouling properties [1, 2]. Turkish coastline totals almost about 8400 km. The sponges found in Turkish water, have not been intensively studied yet. During the course of our studies on Turkish marine sponges, we aimed to screen cytotoxic potentials of Agelas oroides Schmidt, Ircinia variabilis Schmidt, Dysidea avara Schmidt, Dictyonella incisa Schmidt, Axinella polypoides Schmidt, Aplysina aerophoba Nardo. Materials were collected from the Turkish coastline of the Aegean Sea as well as the Mediterranean Sea at depths varying from 10 – 30 m. Sponges were cut into small pieces and extracted with methanol. Cytotoxic activity was performed through HeLa (human cervix epithelial cancer cell) by MTT method [3]. All extracts showed concentration dependent cytotoxic activity. IC50 values were found in a range of 159.0 – 823.0 (µg/mL) as given in the table below. Dictyonella incisa was found to be the most active species among all tested sponges. Due to these promising results the samples will be tested on other cancer and non-cancerous cell lines to detect selectivity as a continuing study.

In - vitro and in - vivo antiproliferative activity of Byrsocarpus coccineus (Connaraceae)

The incidence of cancer is on the increase worldwide, and there are concerns of selectivity of action and significant deleterious effects associated with existing anticancer drugs. Based on these facts, tremendous effort is being made worldwide to discover and develop new anticancer agents with better efficacy and safety profile. In this study, various extracts of Byrsocarpus coccineus, a Nigerian medicinal plant, were evaluated for antiproliferative activity in in-vitro and in-vivo assays. The sulforhodamine B (SRB) (in-vitro) using A549 (lung), HCT-116 (colon), PC3 (prostate), A431 (skin), HeLa (cervix), THP-1 (leukemia), NCI-H322 (lung), and COLO-205 (colon) human cancer cell lines, Sarcoma-180 (S-180) ascites and L1210 lymphoid leukemia (in-vivo) antiproliferative assays were used in this study. Based on the standard of 30 µg/mL as the upper IC50 limit for purification of crude extracts, BC-A001 (ethanolic extract; IC50 12 µg/ml with A431); BC-A002 (hydroethanolic extract; IC50 125% considered to depict activity). The results obtained in this study suggest that the extracts of B. coccineus possess significant antitumor activity in-vitro against skin, lung, colon and prostate human cancer cell lines with BC-A002 demonstrating moderate activity in the S-180 ascites model with no activity in the L1210 lymphoid leukemia test.

Facile Fabrication of Near-Infrared-Responsive and Chitosan-Functionalized Cu2 Se Nanoparticles for Cancer Photothermal Therapy.

Photothermal therapy has attracted much interest for use in cancer treatment in recent years. In this study, Cu2 Se nanoparticles as a novel photothermal agent modified by chitosan (CS-Cu2 SeNPs) were successfully synthesized through a facile route at room temperature. The as-synthesized CS-Cu2 SeNPs exhibited good water solubility and significant stability. CS-Cu2 SeNPs can efficiently convert near-infrared (NIR) light into heat and exhibit excellent thermostability. In vitro experiments showed that CS-Cu2 SeNPs had selective cellular uptake between cancer and normal cells and expressed clear anticancer activity on A375 and HeLa human cancer cells. In addition, the anticancer activity was increased to about 400 % by combination with a laser at 808 nm, which acted through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. CS-Cu2 SeNPs irradiated with a laser effectively triggered the intracellular reactive oxygen species (ROS) overproduction that promoted cell apoptosis. Therefore, the developed CS-Cu2 SeNPs could be used as a novel phototherapeutic agent for the photothermal therapy of human cancers.