Caco-2 Tumor Cell Research Articles

Structures and Tumor Cell Lines Proliferation Activities of Triterpenes Isolated from Astilbe grandis.

A total of seven compounds, including four triterpene acids and three triterpene lactones, were isolated from the ethanolic extract of the roots of Astilbe grandis Stapf ex Wils. Two of the triterpene lactones (1-2) were never reported before and compounds 3-5 were isolated for the first time from the plant. The structures of these compounds were all identified by spectroscopic analysis. Compounds 1-2 were analyzed by 2D NMR and their absolute configurations were determined using experimental CD in comparison with calculated ECD values. The structure of compound 1 was also further confirmed by single crystal X-ray diffraction analysis. The cytotoxicity of compounds 1-7 on A549, Caco-2, H460 and Skov-3 tumor cells were all evaluated using CCK-8. They all exhibited positive inhibitory effects on Caco-2 tumor cells with IC50 less than10 μM, while the inhibitory effects on H460 tumor cells were more moderate. Unfortunately, they displayed little apparent cytotoxicity to the other two types of cells.

Design, Synthesis, and Anti-tumor Activity of Novel 2-Aryl Benzimidazole Compounds.

Combretastatin A-4 (CA-4) is a natural product isolated from the bark of the South African bush willow tree Combretum caffrum, which exerts tubulin inhibition, but its clinical application is limited due to poor stability and water solubility. 2-aryl benzimidazoles are excellent pharmacological skeletons with many activities, especially in tumor inhibition, and better pharmacokinetic properties. Several scaffold CA-4 analogs have been synthesized to date possessing antitumor activities. The benzimidazole was applied as the core moiety to replace the B ring and unstable linkage of CA-4, and the 5-aryl acetenyl group was introduced to improve the antitumor activity. MCF-7, A549, Caco-2, Siha, and Eca-109 tumor cell lines were used to study inhibition by these agents in vitro. The benzimidazole structure was constructed from the oxidation of o-nitroaniline and aldehyde and the following schemes, and the structural characterization was carried out. The antitumor effects were evaluated in vitro through MTT assay, cell cycle arrest, and apoptosis assay. Molecular docking with tubulin (Protein ID: 1SA0) was analyzed for the structure-activity relationship. Among these derivatives, 4a-4h series (with 6-methoxy group) compounds inhibited the tumor cell lines much stronger than the CA-4 and cisplatin, especially compound 4f showed prominently inhibitory activity in Siha cell with IC50 value as 0.61 μmol/L. The further assay showed that the cell cycle was arrested at the G0/G1 phase as well verified in apoptosis assay. Molecular docking indicated that 4f had stronger affinity energy and hydrogen bond than CA-4. The compound 4f has the potency to be used as an anti-tubulin agent and the 2-trimethoxyphenyl benzimidazole skeleton deserves further study as an antitumor structure.

Narcissus pseudonarcissus L. (Amaryllidaceae) bulb metabolite profiling and biological activities

Various metabolomics approaches have greatly contributed to the study of natural products from medicinal plants. Among thousands of plant species, Narcissus pseudonarcissus L. (Amaryllidaceae) is reputed for its ornamental, industrial, and medicinal applications. This plant is also used traditionally for microbial infections, inflammations, skin complaints, and cancers. Long ago, N. pseudonarcissus has gained considerable research interest thanks to its diverse alkaloids that have been widely studied. However, the non-alkaloidal principles and different bioactivities of this plant were poorly deliberated in previous works. Therefore, this work evaluates the biological potential of N. pseudonarcissus bulbs′ total ethanol extract (TEE) and its derived fractions (I‒IV), along with exploring the overlooked non-alkaloidal metabolites of this amaryllid. Overall, GC‒MS-based analysis of the bulbs led to the identification of varied metabolites, e.g., long-chain alkyl amines, alkylbenzenes, long-chain hydrocarbons, fatty acid derivatives, and phenylpropanoids. Most of these phytochemicals are first characterized herein in either the genus Narcissus or the family Amaryllidaceae. Additionally, the acidic EtOAc fraction (II) exhibited the highest scavenging potential of the 2,2′-diphenyl-1-picrylhydrazyl radical and the greatest ferric reducing power, possibly due to its relatively higher contents of phenolics and flavonoids that were also estimated herein. On the other hand, the basic EtOAc fraction (III) exerted the maximum anti-proliferative actions against Caco-2 (colon) and Mcf-7 (breast) tumor cells, while all of the tested fractions were inactive against HepG-2 (liver) cancer cells. Finally, different N. pseudonarcissus fractions demonstrated varied inhibitory activities against a group of pathogenic bacteria and fungi. Among them, fractions II and III were further observed as good synergists with some standard antimicrobial agents, even against some resistant microbial strains. These data could support the reported use of N. pseudonarcissus in traditional medical systems and help widen its future phytochemical and biological prospection.

Metabolomics of the secondary metabolites of Ammi visnaga L. roots (family Apiaceae) and evaluation of their biological potential

Recent scientific advancements in biotechnological, nanobiotechnological, and omics approaches have blossomed into a plethora of applications that hold the potential to revolutionize natural product-based drug discovery. In this context, the present work was undertaken to unveil the secondary metabolites of the under-explored roots of Ammi visnaga L. (family Apiaceae) using HPLC‒HESI‒HRMS-based metabolomics, along with evaluating their anti-proliferative potential against a number of tumor cells in comparison with their green synthesized silver nanoparticles (SNPs), for the first time. Overall, the total ethanol extract of A. visnaga roots (TEEAVR) revealed potent inhibitory actions against colon cancer (Caco-2), breast cancer (Mcf-7), and hepatocellular carcinoma (HepG-2) cell lines, with IC50 values of 3.19 ± 0.07, 12.36 ± 0.13, and 18.38 ± 0.09 µg/mL, respectively. More interestingly, the prepared biogenic SNPs of TEEAVR exhibited more prominent inhibitory potential, particularly against Caco-2 tumor cells (IC50= 0.24 ± 0.05 µg/mL), which was even higher than that of doxorubicin (IC50= 2.12 ± 0.04 µg/mL). Moreover, HPLC‒HESI‒HRMS metabolic profiling of TEEAVR resulted in the characterization of a group of chemically varied metabolites, including phenylpropanoids, flavonoids, isobenzofuranones, coumarins, and chromones. Among them, junipediol A 4-O-glucoside (1a), junipediol A 8-O-glucoside (1b), acacetin (2), and apiumetin-O-glucoside (7) exhibited greater binding affinities to the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase compared to the reference drug, erlotinib; suggesting their possible contribution as EGFR inhibitors to the promising anti-proliferative properties of TEEAVR. These findings cast a new light on the metabolic diversity of A. visnaga roots as an overlooked underground treasure of pharmaceutically relevant phytochemicals that could be incorporated into future anticancer drug research.

Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A.

Here, we report on the synthesis of libraries of new 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones 3 (twenty-two compounds) and new 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones 5 (twenty-four compounds) with stereo controlled Z-geometry under microwave irradiation. The 46 designed final compounds were tested in order to determine their activity against four representative protein kinases (DYR1A, CK1, CDK5/p25, and GSK3α/β). Among these 1,3-thiazolidin-4-ones, the molecules (5Z) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC50 0.028 μM) and (5Z)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5H)-one 5s (IC50 0.033 μM) were identified as lead compounds and as new nanomolar DYRK1A inhibitors. Some of these compounds in the two libraries have been also evaluated for their in vitro inhibition of cell proliferation (Huh7 D12, Caco2, MDA-MB 231, HCT 116, PC3, and NCI-H2 tumor cell lines). These results will enable us to use the 1,3-thiazolidin-4-one core as pharmacophores to develop potent treatment for neurological or oncological disorders in which DYRK1A is fully involved.

PLA-PEG nanospheres decorated with phage display selected peptides as biomarkers for detection of human colorectal adenocarcinoma.

Peptide-mediated targeting to colorectal cancer can increase selectivity and specificity of this cancer diagnosis acting as biomarkers. The present work aimed to select peptides using the phage display technique and associate the peptides with polymeric nanospheres in order to evaluate their cytotoxicity and selectivity during cell interaction with Caco-2 human colon tumor cell line. Two peptides identified by phage display (peptide-1 and peptide-2) were synthesized and exhibited purityhigher than 84%. Poly(lactic acid)-block-polyethylene glycol nanospheres were prepared by nanoprecipitation and double emulsion methods in order to load the two peptides. Nanoparticles ranged in size from 114 to 150nm and peptide encapsulation efficiency varied from 16 to 32%, depending on the methodology. No cytotoxic activity was observed towards Caco-2 tumor cell line, either free or loaded peptides in concentrations up to 3μM at incubation times of 6 and 24h, indicating safety as biomarkers. Fluorescein isothiocyanate-labeled peptides allowed evaluating selective interactions with Caco-2 cells, where peptide-1 entrapped in nanospheres showed greater intensity of co-localized cell fluorescence, in comparison to peptide-2. Peptide-1 loaded in nanospheres revealed promising to be investigated in further studies of selectivity with other human colon rectal cells as a potential biomarker.Graphical abstract.

Fungal-Mediated Biotransformation of Soybean Supplemented with Different Cereal Grains into a Functional Compound with Antioxidant, Anti-Inflammatory and Antitumoral Activities

The aim of this study was to select fungal strains and alternative substrates to increase the production of bioactive compounds by solid-state bioprocessing using soybeans. Initially, from a total of 17 fungi strains, R. oligosporus NRRL 3267, R. oligosporus NRRL 2710, and R. arrhizus NRRL 2582 were pre-selected for presenting the greatest antioxidant activities during soybean fermentation. The three Rhizopus strains were cultured in soybeans supplemented with different cereal grains (brown rice, wheat, corn, and oat) aiming to achieve a higher antioxidant activity. Soybean supplementation with brown rice increased the concentration of phenolic compounds (0.697 to 6.447 mg GAE g-1) significantly compared with the only use of soybean (1.792 to 3.10 mg GAE g-1), using R. oligosporus NRRL 2710. The improved fungal-mediated biotransformation process (R. oligosporus NRRL 2710 with soybeans and brown rice) generated an isoflavone aglycone-rich product, containing different antioxidant compounds, such as trans-cinnamic acid, gallic acid, myricetin, quercetin, and kaempferol. The fermented substrate also showed great potential to inhibit hyaluronidase enzyme (anti-inflammatory activity) and against CaCo-2 tumor cells growth (antitumor activity). The resulting compound could serve as a value-added food and/or feed ingredient and a rich source of bioactive compounds.

Synthesis and anticancer activity of novel pyrazolo[4′,3′:5,6]pyrano[2,3-d] pyrimidin-5(2H)-one derivatives

Abstract A novel sequence of pyrazole connected pyrano[2,3-d]-pyrimidin-5(2H)-one derivatives (6a-j) were designed, prepared and screened for their cytotoxicity against four human cancer cell lines like MCF-7 (breast), HeLa (cervical), CaCo2 (colorectal) and HepG2 (liver) by MTT assay. Most of the tested molecules were exhibited good to excellent cytotoxicity against all tested cell lines when compared to the standard drug Doxorubicin. Amongst all the synthesized target compounds, the molecules (7e & 7d) exhibited the excellent anticancer activity against all the human MCF-7, HeLa, CaCo2 and HepG2 tumor cell lines, with the inhibitory concentration (IC50) values of 14, 14, 13, & 16 μg mL−1 and 16, 14, 15 & 17 μg mL−1, respectively, while, molecules (7f & 7i) revealed good inhibitory activity against all screened cell lines with the IC50 values of 22, 25, 25 & 24 μg mL−1 and 21, 20, 21, & 20 μg mL−1. All the novel target molecules were determined and characterized by various spectroscopic (1H NMR, 13C NMR and HR-MS) analysis.

Anticancer study of heterobimetallic platinum(II)-ruthenium(II) and platinum(II)-rhodium(III) complexes with bridging dithiooxamide ligand

Three heterobimetallic platinum (II)/ruthenium (II) and platinum (II)/rhodium (III) complexes, A: Pt{S–S2C2(NR)2H}{μ-S2C2(NR)2}-[Ru (p-cymene)Cl], R = isoamyl; B: Pt{S–S2C2(NR)2H}{μ-S2C2(NR)2}[Rh (phpy)2], R = isoamyl; C: [Pt{S–S2C2(NR)2H}{μ-S2C2(NR)2}-[Rh(C5Me5)Cl]], R = benzyl, were prepared from mononuclear complexes 1 and 2, 1: [Pt (H-isoamyl2DTO)2]; 2: [Pt (H-benzyl2DTO)2], DTO = dithiooxamide, by reaction of 1 or 2 with the corresponding chlorido-bridged dimers, [Rh(C5Me5)Cl (μ-Cl)]2, [Ru (p-cymene)Cl (μ-Cl)]2 or [Rh (phpy)2 (μ-Cl)]2, and then evaluated as anticancer agents for the inhibition of the three proteolytic activities of human 20S proteasome, one of the main target for cancer therapy. These complexes were also screened for the inhibition of a couple of human cathepsins known to be involved in metastatic processes. A-C turned out to be active towards these enzymes. In addition, they showed in vitro antiproliferative activity against neuroblastoma SH-SY5Y, melanoma SK-Mel-28, hepatocellular adenocarcinoma HepG2 and colorectal adenocarcinoma Caco-2 tumor cell lines, without any sign of cytotoxicity in primary human fibroblasts WI-38. Moreover, these complexes induced apoptosis in the former tumor cell line, as displayed by cytofluorimetric analyses. This study indicated that these compounds may represent valuable lead structures for the development of new anticancer agents.

Synthesis and in vitro evaluation of the antitumoral phototherapeutic potential of squaraine cyanine dyes derived from indolenine

In this work several symmetrical indolenine squaraine dyes with different groups positioned on the four-membered central ring, such as sulfur, barbituric acid, amino and methylamino, were synthesized, and their structures were fully characterized. All dyes displayed intense and narrow absorption bands in the visible region. To evaluate their singlet oxygen formation ability, the 1,3-diphenylisobenzofuran assay was used. The degradation of these squaraine dyes upon light exposure was evaluated in order to infer about their photostability. The in vitro potential of these compounds as photosensitizers for photodynamic therapy was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in several tumor (Caco-2, MCF-7 and PC-3) and non-tumor (NHDF and N27) cell lines, using a custom-built LED based light exposure system emitting radiation with the central wavelength close to the maximum absorption wavelength of the squaraine dyes. The indolenine squaraine dyes showed a high ability to produce singlet oxygen and good photostability. The zwitterionic dyes, namely the unsubstituted dye, the barbituric acid derivative and the monothiosquaraine dye, showed relevant photodynamic activity. It was noteworthy that the unsubstituted squaraine dye exhibited a cytotoxic selectivity for the Caco-2 tumor cell line when compared to the NHDF normal cell line.

Natural CAC chemopreventive agents from Ilex rotunda Thunb.

Colitis-associated cancer (CAC) is one of the most serious complications of inflammatory bowel disease. The pathogenesis of CAC is complicated and so far elusive, and the anti-inflammatory effect does not assure CAC preventive activity, making it difficult to discover CAC preventive drugs. In this study, we report the CAC preventive effect of the ethyl acetate (EIR) of Ilex rotunda Thunb., a traditional Chinese herbal medicine being clinically used to treat intestinal disease. We also report the results of screening for CAC preventive agents from EIR via a nuclear factor-kappa B (NF-κB) translocation model in Caco2 cells, since activated NF-κB can be used by tumor cells at the early stage of tumorigenesis. Twenty-four components were isolated from EIR and identified by multiple chromatography and spectral analysis. MTT experiments in IEC-6 and RAW264.7 cells showed that all 24 compounds were toxic-free to normal cell lines. Furthermore, compound rotundic acid (RA) (19) exhibited an inhibitory effect on LPS-induced NF-κB translocation in Caco2 cells. Moreover, RA did not induce apoptosis in Caco2 tumor cells while possessing an anti-inflammatory effect both in immune and intestinal epithelium cells (RAW264.7 and IEC-6 cells, respectively). Removing RA (19) and its 28-O-glucopyranoside (17) from EIR definitely undermined the in vivo CAC preventive activity of EIR. Therefore, the current study suggested that RA (19) could be a potential therapeutic agent against CAC.

The Use of Human, Bovine, and Camel Milk Albumins in Anticancer Complexes with Oleic Acid.

Oleic acid (OA) is a monounsaturated fatty acid that upon binding to milk proteins, such as α-lactalbumin and lactoferrin, forms potent complexes, which exert selective anti-tumor activity against malignant cells but are nontoxic for healthy normal cells. We showed that the interaction of OA with albumins isolated from human, bovine, and camel milk results in the formation of complexes with high antitumor activity against Caco-2, HepG-2, PC-3, and MCF-7 tumor cells. The antitumor effect of the complexes is mostly due to the action of oleic acid, similar to the case of OA complexes with other proteins. Viability of tumor cells is inhibited by the albumin-OA complexes in a dose dependent manner, as evaluated by the MTT assay. Strong induction of apoptosis in tumor cells after their treatment with the complexes was monitored by flow cytometry, cell cycle analysis, nuclear staining, and DNA fragmentation methods. The complex of camel albumin with OA displayed the most pronounced anti-tumor effects in comparison with the complexes of OA with human and bovine albumins. Therefore, these results suggest that albumins have the potential to be used as efficient and low cost means of tumor treatment.

Synthesis, characterization, anticancer and antimicrobial study of arene ruthenium(II) complexes with 1,2,4-triazole ligands containing an α-diimine moiety

Abstract The reaction of the ruthenium arene dimers [(η 6-arene)Ru(μ-Cl)Cl]2 (where arene=benzene or p-cymene) with the ligands 4-benzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L1 ), 2-methoxybenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L2 ), 4-methylbenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L3 ) and indole-3-carbaldehyde-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L4 ) in a 1:2 ratio gives the new complexes [(η 6-arene)RuCl(L)]+ [arene=C6H6 (with L=L1(1), L2(3), L4(7), with PF6 − as a counter ion, and L4 (6), with Cl− as a counter ion) or p-cymene with L=L1(2), L2(4), L3(5), L4(8) with PF6 − as a counter ion]. All complexes were fully characterized using 1H and 13C NMR, elemental analyses, UV/Vis and IR spectroscopy. The single crystal X-ray structures of ligand L2 and complex 1 have been determined. The structure of 1 has the Ru atom coordinated with the arene group and to the N,N′-bidentate ligand and to the Cl atom. The arene group occupies the apex, while the ligand and the Cl atom are at the base of a pseudo-octahedral three-legged piano stool. The cytotoxicity of these mononuclear complexes was established in the human epithelial colorectal adenocarcinoma cell line (Caco-2) and for selectivity in the non-cancerous human embryonic kidney cell line (HEK293), using 5-fluorouracil (5-FU) as the reference anticancer drug. Compounds 1 and 7 were relatively inactive toward the Caco-2 tumor cells (IC50>200), while complexes 2–5 showed moderate anti-proliferative properties (IC50>100–200). Compound 6, however, displayed better anti-proliferative properties with an IC50 value lower than that of the reference drug, 5-FU, and was therefore further investigated for its antimicrobial activity against six Gram-positive and four Gram-negative bacteria.

Synthesis, characterization, antiproliferative, and antimicrobial activity of osmium(II) half-sandwich complexes

New osmium(II)-arene complexes [(η6-C6H6)OsCl(C5H4N-2-CH=N-C6H5X)](PF6) (X = p-flouro (1), p-chloro (2), p-methyl (3)) were synthesized by reaction of the corresponding bidentate N,N′-ligands with the osmium-arene precursor [(η6-C6H6)Os(μ-Cl)Cl]2 in a 2:1 ratio. These complexes were characterized by UV–Vis, IR, 1H, 13C NMR spectroscopy, and elemental analysis and, for compound 1, a single crystal X-ray structure was also obtained. The complexes were investigated for antiproliferative activity in vitro against MCF-7 (human breast adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), and HepG2 (human hepatocellular carcinoma) tumor cell lines. To test their selectivity, the non-tumor HEK293 (human embryonic kidney) cell line was used. The compounds were selective toward the tumor cell lines when compared to the known anticancer drug 5-fluorouracil which displayed low selectivity. The compounds were substantially more active against Caco-2 than 5-fluorouracil. They also showed moderate activity against the other two tumor cell lines. In addition, the antimicrobial activity of complex 2 was explored against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Complex 2 showed anti-mycobacterial activity against Mycobacterium smegmatis and bactericidal activity against drug-resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.

Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity.

The present study aimed to explore the cytotoxic effect of ortho- and para-positional isomers of thiophene acetyl salicylic acid esters against cancer and normal cell lines. Two new thiophene-2-acetic acid esters (2-((2-(thiophen-2-yl)acetyl)thio)benzoic acid and 4-((2-(thiophen-2- yl)acetyl)thio)benzoic acid) were synthesized and characterized by Elemental analysis, Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance (NMR), 13C-NMR and High-resolution mass spectroscopy. The compounds were tested for their in vitro cytotoxic activity against A549 and Caco2 tumor cell lines and CCD- 19Lu and CCD 841 CoN normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,4,diphenyltetrazolium bromide assay. 2-((2-(thiophene-2-yl)acetyl)thio)benzoic acid showed a higher activity with (IC50 = 239.88µM/mL) compared with a reference drug nearly as active as cyclophosphamide (IC50 = 257.11 µM/mL) on Caco2 cell line. Apoptosis was observed by flow cytometric analysis on Caco2 cells. Thus, positional isomerism is critical for the pharmacological properties of thiophene acetyl salicylic acid esters against colon cancer cell line compared with nonsmall cell lung cancer cell line. The ortho-isomer induced cell death and was much more potent than the para-isomer.

Phytochemical Analysis with Antioxidant and Cytotoxicity Studies of the Bioactive Principles from Zanthoxylum capense (Small Knobwood).

Zanthoxylum capense (small knobwood) is a South African species known for a wide range of anecdotal uses. However, there is a dearth of information on its phytoconstitutional make-up, specifically its knobs, with only a few reports on the bioactive compounds that could justify its ethnomedicinal use. This work aimed to identify the active principles in Z. capense and evaluate their cytotoxicity against breast cancer tumor cells. Extracts from the stem bark, knobs and leaves were purified using chromatographic methods and characterized using spectroscopic techniques. Cytotoxicity of isolated compounds was evaluated on mammalian MCF-7, Caco-2 tumor cell lines and HEK295, a normal kidney cell line. The following compounds were isolated from the plant: a quaternary benzophenanthridine-type alkaloid (chelerythrine) along with its alkanoamine derivative (6-hydroxydihydrochelerythrine), an indolopyridoquinazoline alkaloid (rutaecarpine), an alkyl p-coumaric acid ester (dodecyl-trans-p-coumarate), a lignan (sesamin), a flavanol (catechin), two triterpenoids (lupeol and sitosterol) and two pigments (pheophytin a and lutein). In the cytotoxicity study, all tested samples decreased the viability of the MCF-7 tumor cells by at least 23% at concentration 1 μg mL-1 and Caco-2 tumor cells by at least 15% at concentration 5 μg mL-1 but a mild toxic effect on HEK295 across the tested samples. The following compounds were isolated from the plant: a quaternary benzophenanthridine-type alkaloid (chelerythrine) along with its alkanoamine derivative (6-hydroxydihydrochelerythrine), an indolopyridoquinazoline alkaloid (rutaecarpine), an alkyl p-coumaric acid ester (dodecyl-trans-p-coumarate), a lignan (sesamin), a flavanol (catechin), two triterpenoids (lupeol and sitosterol) and two pigments (pheophytin a and lutein). In the cytotoxicity study, all tested samples decreased the viability of the MCF-7 tumor cells by at least 23% at concentration 1 μg mL-1 and Caco-2 tumor cells by at least 15% at concentration 5 μg mL-1 but a mild toxic effect on HEK295 across the tested samples.

Synthesis of Novel Hybrids Inspired from Bromopyrrole Alkaloids Inhibiting MMP-2 and -12 as Antineoplastic Agents.

Synthesis of novel set of forty semicarbazide/thiosemicarbazide hybrids inspired from marine bromopyrrole alkaloids is reported. Biological screening of these hybrids against a panel of five human cancer cell lines identified a number of hits endowed with interesting cytotoxicity profile. Compounds 5c and 5e (IC50 =0.03μm), 5t (IC50 =0.03μm), 4s (IC50 =0.07μm), and 5n (IC50 =0.01μm) displayed maximum cytotoxicity toward hormone-dependent breast cancer cells MCF7, hepatic cancer cells WRL68, colon cancer cells CaCO2 and mouth and oral cancer cells KB403, respectively. The most active hits were further investigated for their potential to inhibit MMP-2 and MMP-12. Compound 5e showed maximum activity (IC50 =1.8μm) toward MMP-2. Further, we preformed anti-invasive assay on the most active compounds, where CaCO2 tumor cell migration was significantly decreased (77.9%) by hybrid 5e. The non-toxicity toward human VERO cells (IC50 =83.1 to 231.8μm) indicated the selectivity of most active hits (5c, 5e, 5t and 5n) toward cancer cells.

Starch-based microspheres for sustained-release of curcumin: Preparation and cytotoxic effect on tumor cells

Curcumin (CUR) has been proved to be highly cytotoxic against different tumor cell lines. However, its poor solubility in aqueous medium and fast degradation in physiological pH are the common drawbacks preventing its efficient practical use. Herein, we report the development of original microspheres based on the biopolymer starch crosslinked with N,N-methylenebisacrylamide (MBA) to be applied as an efficient delivering system for CUR. The starch-based microspheres showed high loading efficiency even in loading solution with different CUR concentrations. In vitro release assays data showed that the CUR release is governed by anomalous transport (n=0.73) and it is pH-dependent. Cytotoxicity assays showed that starch microspheres could improve the cytotoxicity of CUR toward Caco-2 and HCT-116 tumor cell lines up to 40 times than that found for pure CUR. This behavior was attributed to the slowly and sustained release of CUR from the microspheres.

NOX1 participates in ROS-dependent cell death of colon epithelial Caco2 cells induced by Entamoeba histolytica

Entamoeba histolytica, which causes amebic colitis and occasional liver abscesses in humans, can induce host cell death through apoptosis and necrosis. Recently, we have demonstrated that E. histolytica can induce cell death in neutrophils via diphenyleneiodonium-sensitive NADPH oxidase (NOX)-derived reactive oxygen species (ROS). Although there are enzyme systems similar to the phagocyte NADPH oxidase system in many non-phagocytic cell types, the signaling role of NOX-derived ROS in cell death of human colon epithelial cells induced by E. histolytica remains obscure. Incubation of colon epithelial Caco2 tumor cell lines with amebic trophozoites resulted in intracellular ROS generation and cell death in a caspase-independent manner. Pretreatment with DPI, an inhibitor of NOX, strongly decreased E. histolytica-induced cell death in Caco2 cells. As identified by RT-PCR, NOX1 transcripts were highly expressed in Caco2 cells. siRNA-mediated suppression of NOX1 protein significantly inhibited E. histolytica-induced cell death and ROS response in Caco2 cells. These results suggest that NOX1 participates in the ROS-dependent cell death of colon epithelial cells induced by amebic adhesion during the early phase of intestinal amebiasis.

Synthesis, structure and antitumor activity of [RhCl 3(N–N)(DMSO)] polypyridyl complexes

The [RhCl 3(N–N)(DMSO)] complexes, the N–N being 2,2′-bipyridine ( 1), 1,10-phenanthroline ( 2), 4,7-diphenyl-1,10-phenanthroline ( 3), 4,4′-dimethyl-2,2′-bipyridine ( 4) and 1,10-phenanthroline-5,6-dione ( 5), have been synthesized and characterized with spectroscopic methods. The compounds 2– 5 adopt mer- and complex 1 fac-structure. The molecular and electronic structure studies of mer- and fac-complexes with bpy and phen ligands at the DFT B3LYP level with 3-21G ∗∗ basis set showed that mer-isomers are more stable. The cytostatic activity of the [RhCl 3(N–N)(DMSO)] complexes against Caco-2 and A549 tumor cells have been studied. Their antibacterial activity have also been investigated. It has been found that the very promising biological activity show complexes 2, 3 and 4.