scholarly journals In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 148 ◽  
Author(s):  
Van Tran ◽  
Jitka Viktorova ◽  
Katerina Augustynkova ◽  
Nikola Jelenova ◽  
Simona Dobiasova ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
In Silico ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
In Vitro Cytotoxicity ◽  
Biologically Relevant ◽  
Ic50 Values ◽  
Epithelial Cell Layer ◽  
Pre Treatment

Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.

scholarly journals A New NT4 Peptide-Based Drug Delivery System for Cancer Treatment

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1088 ◽  
Author(s):  
Jlenia Brunetti ◽  
Sara Piantini ◽  
Marco Fragai ◽  
Silvia Scali ◽  
Giulia Cipriani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Tumor Targeting ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
In Vitro Cytotoxicity ◽  
Cancer Tissue ◽  
Chemotherapy Drugs

The development of selective tumor targeting agents to deliver multiple units of chemotherapy drugs to cancer tissue would improve treatment efficacy and greatly advance progress in cancer therapy. Here we report a new drug delivery system based on a tetrabranched peptide known as NT4, which is a promising cancer theranostic by virtue of its high cancer selectivity. We developed NT4 directly conjugated with one, two, or three units of paclitaxel and an NT4-based nanosystem, using NIR-emitting quantum dots, loaded with the NT4 tumor-targeting agent and conjugated with paclitaxel, to obtain a NT4-QD-PTX nanodevice designed to simultaneously detect and kill tumor cells. The selective binding and in vitro cytotoxicity of NT4-QD-PTX were higher than for unlabeled QD-PTX when tested on the human colon adenocarcinoma cell line HT-29. NT4-QD-PTX tumor-targeted nanoparticles can be considered promising for early tumor detection and for the development of effective treatments combining simultaneous therapy and diagnosis.

scholarly journals Antiproliferative Activity of Stokesia laevis Ethanolic Extract in Combination with Several Food-Related Bioactive Compounds; In Vitro (Caco-2) and In Silico Docking (TNKS1 and TNKS2) Studies

2021 ◽  
Vol 11 (21) ◽  
pp. 9944
Author(s):  
Georgeta Neagu ◽  
Amalia Stefaniu ◽  
Adrian Albulescu ◽  
Lucia Pintilie ◽  
Lucia Camelia Pirvu
Keyword(s):  
Bioactive Compounds ◽  
Antiproliferative Activity ◽  
In Silico ◽  
Molecular Targets ◽  
Tumor Cell Line ◽  
Ethanolic Extract ◽  
Human Colon ◽  
In Silico Docking ◽  
Ic50 Values

This study evaluates in vitro cytotoxic and antiproliferative activity on human colon tumor cell line Caco-2 (ATCC-HTB-37) of a standardized (5 mg GAE/mL) ethanolic extract from Stokesia laevis (Slae26), of five polyphenols compounds (reference substances, ref.), namely luteolin-7-O-glucoside, luteolin-8-C-glucoside, caffeic acid, gentisic acid, and p-aminobenzoic acid (PABA), as well as of Slae26 combinations with the five reference substances, 1:1 mass rate (GAE, ref.). Cell viability studies (MTS test) have revealed IC50 values of 36 μg GAE/mL in the case of Slae26 ethanolic extract, while Slae26 combinations with the five phenolics indicated IC50 values around 5 μg GAE/mL. In silico docking studies on the molecular targets human tankyrase 1 (TNKS1) and human tankyrase 2 (TNKS2) in complex with their native ligands, Co-crystallized 3J5A and Co-crystallized FLN, indicated score values of −104.15 and −76.97, respectively; in the series of the reference compounds studied, luteolin-7-O-glucoside was revealed with the best score values on both molecular targets (−80.49 and −85.17), together signifying real antiproliferative potential against human colon cancer of Slae26, of luteolin-7-O-glucoside, and of Slae26 combinations with all food-related bioactive compounds tested.

In Vitro and in Vivo Comparison of Binding of 99m-Tc-Iabeled Anti-CEA MAb F33-104 with 99m-Tc-labeled Anti-CEA MAb BW431/26

1999 ◽  
Vol 38 (04) ◽  
pp. 115-119
Author(s):  
N. Oriuchi ◽  
S. Sugiyama ◽  
M. Kuroki ◽  
Y. Matsuoka ◽  
S. Tanada ◽  
...  
Keyword(s):  
Nude Mice ◽  
Binding Capacity ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Cell Binding ◽  
Vitro Binding ◽  
Labeling Method ◽  
Human Colon Adenocarcinoma

Summary Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tclabeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 107 of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tcactivity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

scholarly journals New Antiproliferative Triflavanone from Thymelaea hirsuta—Isolation, Structure Elucidation and Molecular Docking Studies

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 739
Author(s):  
Sameh S. Elhady ◽  
Reda F. A. Abdelhameed ◽  
Mayada M. El-Ayouty ◽  
Amany K. Ibrahim ◽  
Eman S. Habib ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Tumors ◽  
Fold Increase ◽  
In Vitro Cytotoxicity ◽  
Mitogen Activated Protein Kinase ◽  
Wild Plant ◽  
Cytotoxic Activities ◽  
Ic50 Values ◽  
Thymelaea Hirsuta

In this study isolates from Thymelaea hirsuta, a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (1), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea: daphnoretin methyl ether (2), rutamontine (3), neodaphnoretin (4), acetyldaphnoretin (5), and edgeworthin (6); two flavonoids: genkwanin (7) and trans-tiliroside (8); p-hydroxy benzoic acid (9) and β sitosterol glucoside (10). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1, 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.

scholarly journals In Vitro and In Silico Anti-Arboviral Activities of Dihalogenated Phenolic Derivates of L-Tyrosine

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3430
Author(s):  
Vanessa Loaiza-Cano ◽  
Laura Milena Monsalve-Escudero ◽  
Manuel Pastrana Restrepo ◽  
Diana Carolina Quintero-Gil ◽  
Sergio Andres Pulido Muñoz ◽  
...  
Keyword(s):  
Cell Line ◽  
Viral Protein ◽  
In Silico ◽  
Public Health Problem ◽  
Cellular Proteins ◽  
Vero Cell Line ◽  
Viral Particles ◽  
Pre Treatment ◽  
Line Infection

Despite the serious public health problem represented by the diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses, there are still no specific licensed antivirals available for their treatment. Here, we examined the potential anti-arbovirus activity of ten di-halogenated compounds derived from L-tyrosine with modifications in amine and carboxyl groups. The activity of compounds on VERO cell line infection and the possible mechanism of action of the most promising compounds were evaluated. Finally, molecular docking between the compounds and viral and cellular proteins was evaluated in silico with Autodock Vina®, and the molecular dynamic with Gromacs®. Only two compounds (TDC-2M-ME and TDB-2M-ME) inhibited both ZIKV and CHIKV. Within the possible mechanism, in CHIKV, the two compounds decreased the number of genome copies and in the pre-treatment strategy the infectious viral particles. In the ZIKV model, only TDB-2M-ME inhibited the viral protein and demonstrate a virucidal effect. Moreover, in the U937 cell line infected with CHIKV, both compounds inhibited the viral protein and TDB-2M-ME inhibited the viral genome too. Finally, the in silico results showed a favorable binding energy between the compounds and the helicases of both viral models, the NSP3 of CHIKV and cellular proteins DDC and β2 adrenoreceptor.

scholarly journals Antiproliferative Activity on Human Colon Adenocarcinoma Cells and In Vitro Antioxidant Effect of Anthocyanin-Rich Extracts from Peels of Species of the Myrtaceae Family

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 564
Author(s):  
Nayara Simas Frauches ◽  
Júlia Montenegro ◽  
Thuane Amaral ◽  
Joel Pimentel Abreu ◽  
Gabriela Laiber ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Phenolic Compounds ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Native Plant ◽  
Total Anthocyanin ◽  
Adenocarcinoma Cells ◽  
Human Colon Adenocarcinoma ◽  
Colon Adenocarcinoma Cells

There is a significant indication of the beneficial health effects of fruit rich diets. Fruits of native plant species have noticeably different phytochemicals and bioactive effects. The aim of this work was to characterize and compare the constituents of jabuticaba (Myrciaria jaboticaba, MJ), jamun-berry (Syzygium cumini, SC), and malay-apple (Syzygium malaccense, SM) extracts and their influence on antioxidant activity in vitro and antiproliferative effects on human colon adenocarcinoma cells. According to the results, dried peel powders (DP) have a high anthocyanin content, phenolic compounds, and antioxidant activity when compared to freeze dried extracts (FD). M. jaboticaba dried peel powder extract had a higher total anthocyanin and phenolic compounds content (802.90 ± 1.93 and 2152.92 ± 43.95 mg/100 g, respectively). A reduction in cell viability of HT-29 cells after treatment with M. jaboticaba extracts (DP-MJ and FD-MJ) was observed via MTT assay. Flow cytometry showed that the treatment with the anthocyanin-rich extracts from MJ, SC, and SM had an inhibitory impact on cell development due to G2/M arrest and caused a rise in apoptotic cells in relation to the control group. The findings of this study highlight the potential of peel powders from Myrtaceae fruits as an important source of natural antioxidants and a protective effect against colon adenocarcinoma.

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