The objective of the present study was to evaluate the in vitro and in vivo anti-cancer effect of Nigella sativa L. seed extracts. The essential oil (IC 50 = 0.6%, v/v) and ethyl acetate (IC 50 = 0.75%) extracts were more cytotoxic against the P815 cell line than the butanol extract (IC 50 = 2%). Similar results were obtained with the Vero cell line. Although all extracts had a comparable cytotoxic effect against the ICO1 cell line, with IC 50 values ranging from 0.2 to 0.26% (v/v), tests on the BSR cell line revealed a high cytotoxic effect of the ethyl acetate extract (IC 50 = 0.2%) compared to the essential oil (IC 50 = 1.2%). These data show that the cytotoxicity of each extract depends on the tumor cell type. In vivo, using the DBA2/P815 (H 2 d ) mouse model, our results clearly showed that the injection of the essential oil into the tumor site significantly inhibited solid tumor development. Indeed, on the 30th day of treatment, the tumor volume of the control animals was 2.5 ± 0.6 cm 3 , whereas the tumor volumes of the essential oil-treated animals were 0.22 ± 0.1 and 0.16 ± 0.1 cm 3 when the animals were injected with 30 µL (28.5 mg)/mouse and 50 µL (47.5 mg)/mouse per 48 h (six times), respectively. Interestingly, the administration of the essential oil into the tumor site inhibited the incidence of liver metastasis development and improved mouse survival. CorrespondenceA. Zyad
Natural polyphenols extracts have been usually associated with great bioactive properties. In this work, we investigated in vitro antioxidant and antimicrobial potential of the phenolic olive mill wastewater extracts (OWWE) and the olive cake extracts (OCE). Using the Folin Ciocalteux method, OWWE contained higher total phenol content compared to OCE (8.90 ± 0.728 g/L versus 0.95 ± 0.017 mg/g). The phenolic compounds identification was carried out with a performance liquid chromatograph coupled to tandem mass spectrometry equipment (HPLC-ESI-MS). With this method, a list of polyphenols from OWWE and OCE was obtained. The antioxidant activity was measured in aqueous (DPPH) and emulsion (BCBT) systems. Using the DPPH assay, the results show that OWWE was more active than OCE and interestingly the extracts originating from mountainous areas were more active than those produced from plain areas (EC50 = 12.1 ± 5.6 μg/mL; EC50 = 157.7 ± 34.9 μg/mL, resp.). However, when the antioxidant activity was reversed in the BCBT, OCE produced from plain area was more potent than mountainous OCE. Testing by the gel diffusion assay, all the tested extracts have showed significant spectrum antibacterial activity against Staphylococcus aureus, whereas the biophenols extracts showed more limited activity against Escherichia coli and Streptococcus faecalis.
Abstract:Monoterpenes have been identifi ed as responsible of important therapeutic effects of plant-extracts. In this work, we try to compare the cytotoxic effect of six monoterpenes (carvacrol, thymol, carveol, carvone, eugenol and isopulegol) as well as their molecular mechanisms. The in vitro antitumor activity of the tested products, evaluated against fi ve tumor cell lines, show that the carvacrol is the most cytotoxic monoterpene. The investigation of an eventual synergistic effect of the six natural monoterpenes with two anticancer drugs revealed that there is a signifi cant synergy between them (p<5%). On the other hand, the effect of the tested products on cell cycle progression was examined by fl ow cytometry after DNA staining in order to investigate the molecular mechanism of their cytotoxic activity. The results revealed that carvacrol and carveol stopped the cell cycle progression in S phase; however, thymol and isopulegol stopped it in G0/G1 phase. Regarding carvone and eugenol, no effect on cell cycle was observed.
The evaluation of the cytotoxic properties in vitro of three synthetic tripods containing pyrazole: N,N-bis[(3,5-dimethylpyrazol-1-yl)methyl]aniline (1); N,N-tetrakis[(3,5-dimethylpyrazol-1-yl)methyl]-para-phenylenediamine (2); and N,N-tetrakis-[(1,5-dimethylpyrazol-3-yl)methyl]-para-phenylenediamine (3), was examined for their cytotoxic activity on two tumor cell lines: P815 (murin mastocytoma) and Hep (human laryngeal carcinome). While the compound 2 shows a small cytotoxic activity, compounds 1 and 3 are more cytotoxic against both cell lines. However, this cytotoxicity is more pronounced against Hep cell line (IC50: 3.25 microg mL(-1) for compound 1 and 6.92 microg mL(-1) for compound 3) than P815 cell line (IC50: 17.82 microg mL(-1) for compound 1 and 37.21 microg mL(-1) for compound 3). Statistical analysis shows that the compound 1 is two- to threefold more cytotoxic than compound 3 (P < 0.05). Interestingly, the cytotoxicity induced by compound 1 against Hep cell line is more important than that induced by adriamycin used as a positive control.
The present study aims at defining the differential cytotoxicity effect of artemisinin toward P815 (murin mastocytoma) and BSR (kidney adenocarcinoma of hamster) cell lines. Cytotoxicity was measured by the growth inhibition using MTT assay. These in vitro cytotoxicity studies were complemented by the determination of apoptotic DNA fragmentation and Annexin V- streptavidin-FITC assay. Furthermore, we examined the in vitro synergism between artemisinin and the chemotherapeutic drug, vincristin. The in vivo study was investigated using the DBA2/P815 (H2d) mouse model. While artemisinin acted on both tumor cell lines, P815 was much more sensitive to this drug than BSR cells, as revealed by the respective IC50 values (12 µM for P815 and 52 µM for BSR cells). On another hand, and interestingly, apoptosis was induced in P815 but not induced in BSR. These data, reveal an interesting differential cytotoxic effect, suggesting the existence of different molecular interactions between artemisinin and the studied cell lines. In vivo, our results clearly showed that the oral administration of artemisinin inhibited solid tumor development. Our study demonstrates that artemisinin caused differential cytotoxic effects depending not only on the concentration and time of exposure but also on the target cells.
Artemisinin is one of the most widely prescribed drugs against malaria and has recently received increased attention because of its other potential biological effects. The aim of this review is to summarize recent discoveries of the pharmaceutical effects of artemisinin in basic science along with its mechanistic action, as well as the intriguing results of recent clinical studies, with a focus on its antitumor activity. Scientific evidence indicates that artemisinin exerts its biological activity by generating reactive oxygen species that damage the DNA, mitochondrial depolarization, and cell death. In the present article review, scientific evidence suggests that artemisinin is a potential therapeutic agent for various diseases. Thus, this review is expected to encourage interested scientists to conduct further preclinical and clinical studies to evaluate these biological activities.
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