Leaf extracts from Nitraria retusa promote cell population growth of human cancer cells by inducing apoptosis

<p>Abstract</p> <p>Background</p> <p>In this report the phytochemical profile of <it>Nitraria. Retusa (N. Retusa</it>) leaf extracts were identified and their ability to induce apoptosis in human chronic myelogenous erythroleukaemia (K562) was evaluated.</p> <p>Methods</p> <p>Apoptosis of the human chronic myelogenous erythroleukaemia (K562) was evidenced by investigating DNA fragmentation, PARP cleavage and caspases 3 and 8 inducing activities, in the presence of <it>N. retusa </it>extracts.</p> <p>Results</p> <p>Our study revealed that the tested extracts from <it>N. Retusa </it>contain many useful bioactive compounds. They induced in a time-dependent manner the apoptosis the tested cancerous our cell line. This result was confirmed by ladder DNA fragmentation profile and PARP cleavage, as well as a release in caspase-3 and caspase-8 level.</p> <p>Conclusion</p> <p>Our results indicate that the tested compounds have a significant antiproliferative effect which may be due to their involvement in the induction of the extrinsic apoptosic pathway.</p

Evaluation of in vitro antioxidant and apoptotic activities of Cyperus rotundus

AbstractObjectiveTo evaluate in vitro antioxidant and apoptotic activities of Cyperus rotundus (C. rotundus).MethodsThe phytochemical study and the antioxidant activities of both methanol and aqueous extracts from C. rotundus aerial part were determined. In addition, these extracts were also investigated for their cytotoxic and apoptotic activities. The major compound of the methanol extract was isolated. Both methanol and aqueous extracts (300, 150, and 50 μg/mL) were evaluated for their antioxidant activity by the xanthine/xanthine oxidase assay system. However, 16, 8, and 4 mg/mL of each extract were tested to investigate their OH. formation scavenging potential. Aqueous extract (800, 400, and 200 μg/mL) and methanol extract (350, 175, and 88 μg/mL) were tested against lipid peroxidation, induced by 75 μM H2O2. The cytotoxicity (by MTT assay) and cell DNA fragmentation of both extracts were evaluated towards K562 and L1210 cell lines. The major compound was obtained from the butanol fraction of methanol extract and its structure was determined by RMN spectroscopic analysis.ResultsThe methanol and aqueous extracts showed respectively, 88% and 19% inhibition of xanthine oxidase activity. Yet, the same extracts inhibited lipid peroxidation by 61.5% and 42.0%, respectively. Both extracts inhibited OH. formation by 27.1% and 25.3%, respectively. Only methanol extract induced DNA degradation. Orientin was determined as the major compound isolated from the butanol fraction of methanol extract.ConclusionsIt appears that C. rotundus extracts exhibit a potential use as a natural antioxidant and an apoptosis inducer

Essential oil and hydrophilic antibiotic co-encapsulation in multiple lipid nanoparticles: proof of concept and in vitro activity against Pseudomonas aeruginosa

Producción CientíficaIn the worldwide context of an impending emergence of multidrug-resistant bacteria, this research combined the advantages of multiple lipid nanoparticles (MLNs) and the promising therapeutic use of essential oils (EOs) as a strategy to fight the antibiotic resistance of three Pseudomonas aeruginosa strains with different cefepime (FEP) resistance profiles. MLNs were prepared by ultrasonication using glyceryl trioleate (GTO) and glyceryl tristearate (GTS) as a liquid and a solid lipid, respectively. Rosemary EO (REO) was selected as the model EO. REO/FEP-loaded MLNs were characterized by their small size (~110 nm), important encapsulation efficiency, and high physical stability over time (60 days). An assessment of the antimicrobial activity was performed using antimicrobial susceptibility testing assays against selected P. aeruginosa strains. The assays showed a considerable increase in the antibacterial property of REO-loaded MLNs compared with the effect of crude EO, especially against P. aeruginosa ATCC 9027, in which the minimum inhibitory concentration (MIC) value decreased from 80 to 0.6 mg/mL upon encapsulation. Furthermore, the incorporation of FEP in MLNs stabilized the drug without affecting its antipseudomonal activity. Thus, the ability to co-encapsulate an essential oil and a hydrophilic antibiotic into MLN has been successfully proved, opening new possibilities for the treatment of serious antimicrobial infections.Tunisian Ministry of HEducation and Scientific Research and by the Fundación General de la Universidad de Valladolid (PIP 063/147181)Fondo de Innovación, Tecnología y Economía Circular (FITEC) e iNOVA4Health (UIDB/04462/2020

Two calix[4]pyrroles as potential therapeutics for castration-resistant prostate cancer

Macrocyclic compounds meso-(p-acetamidophenyl)-calix[4]pyrrole and meso-(m-acetamidophenyl)-calix[4]pyrrole have previously been reported to exhibit cytotoxic properties towards lung cancer cells. Here, we report pre-clinical in vitro and in vivo studies showing that these calixpyrrole derivatives can inhibit cell growth in both PC3 and DU145 prostatic cancer cell lines. We explored the impact of these compounds on programmed cell death, as well as their ability to inhibit cellular invasion. In this study we have demonstrated the safety of these macrocyclic compounds by cytotoxicity tests on ex-vivo human peripheral blood mononuclear cells (PBMCs), and by in vivo subcutaneous administration. Preliminary in vivo tests demonstrated no hepato-, no nephro- and no genotoxicity in Balb/c mice compared to controls treated with cisplatin. These findings suggest these calixpyrroles might be novel therapeutic tools for the treatment of prostate cancer and of particular interest for the treatment of androgen-independent castration-resistant prostate cancer

Polar extracts from (Tunisian) Acacia salicina Lindl. Study of the antimicrobial and antigenotoxic activities

<p>Abstract</p> <p>Background</p> <p>Methanolic, aqueous and Total Oligomer Flavonoids (TOF)-enriched extracts obtained from the leaves of <it>Acacia salicina </it>'Lindl.' were investigated for antibacterial, antimutagenic and antioxidant activities.</p> <p>Methods</p> <p>The antimicrobial activity was tested on the Gram positive and Gram negative reference bacterial strains. The Mutagenic and antimutagenic activities against direct acting mutagens, methylmethane sulfonate (MMS) and 4-nitro-o-phenylenediamine (NOPD), and indirect acting mutagens, 2-aminoanthracene (2-AA) and benzo[a]pyrene (B(a)P) were performed with <it>S. typhimurium </it>TA102 and TA98 assay systems. In addition, the enzymatic and nonenzymatic methods were employed to evaluate the anti-oxidative effects of the tested extracts.</p> <p>Results</p> <p>A significant effect against the Gram positive and Gram negative reference bacterial strains was observed with all the extracts. The mutagenic and antimutagenic studies revealed that all the extracts decreased the mutagenicity induced by B(a)P (7.5 μg/plate), 2-AA (5 μg/plate), MMS (1.3 mg/plate) and NOPD (10 μg/plate). Likewise, all the extracts showed an important free radical scavenging activity towards the superoxide anion generated by the xanthine/xanthine oxidase assay system, as well as high Trolox Equivalent Antioxidant Capacity (TEAC), against the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS)⁺• radical. TOF-enriched extract exhibited the highest protective effect against free radicals, direct acting-mutagen and metabolically activated S9-dependent mutagens.</p> <p>Conclusions</p> <p>The present study indicates that the extracts from <it>A. salicina </it>leaves are a significant source of compounds with the antimutagenic and antioxidant activities, and this may be useful for developing potential chemopreventive substances.</p

Fraisinib: a calixpyrrole derivative reducing A549 cell-derived NSCLC tumor in vivo acts as a ligand of the glycine-tRNA synthase, a new molecular target in oncology

Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%–90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1.Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-small-cell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition.Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness.Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood–brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases “in one shot.” Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment