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Little is known about the fate, transport, and bioavailability of CeO2 nanoparticles (NPs) in soil. Moreover, there are no reports on the effect of surface coating upon NPs uptake by plants. In this study, Zea mays plants were grown for one month in unenriched and organic soils treated with coated and uncoated CeO2 NPs. In addition, plants were exposed to fluorescein isothiocyanate (FITC)-stained CeO2 NPs and analyzed in a confocal microscope. In organic soil, roots from uncoated and coated NPs at 100, 200, 400, and 800 mg kg−1 had 40, 80, 130, and 260% and 10, 70, 90, and 40% more Ce, respectively, compared to roots from unenriched soil. Conversely, shoots of plants from unenriched soil had significantly more Ce compared with shoots from organic soil. Confocal fluorescence images showed FITC-stained CeO2 NP aggregates in cell walls of epidermis and cortex, suggesting apoplastic pathway. The μXRF results revealed the presence of CeO2 NP aggregates within vascular tissues. To the authors knowledge this is the first report on the effects of surface coating and organic matter on Ce uptake from CeO2 NPs and upon the mechanisms of CeO2 NPs uptake by higher plants

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New stable cationic organogold(III) complexes containing the 'pincer' iminophosphorane ligand (2-C 6 H 4 -PPh 2 =NPh) have been prepared by reaction of the previously described [Au{κ 2 -C,N-C 6 H 4 (PPh 2 =N(C 6 H 5 )-2}Cl 2 ] 1 and a combination of sodium or silver salts and appropriate ligands. The presence of the P atom in the PR 3 fragment has been used as a "spectroscopic marker" to study the in vitro stability (and oxidation state) of the new organogold complexes in solvents like DMSO and water. Compounds with dithiocarbamato ligands and water-soluble phosphines of the general type [Au{κ 2 -C,NC 6 H 4 (PPh 2 =N(C 6 H 5 )-2}(S 2 CN-R 2 )]PF 6 (R = Me 2; Bz 3) and [Au{κ 2 -C,N-C 6 H 4 (PPh 2 =N(C 6 H 5 )-2}(PR 3 ) n Cl]PF 6 (PR 3 = P{Cp(m-C 6 H 4 -SO 3 Na) 2 } n = 1 4, n = 2 TPA {1,3,5-triaza-7-phosphaadamantane} 5) have been synthesized and characterized in solution and in the solid state (the crystal structure of 2 has been determined by X-ray diffraction studies). Complexes 1-5 have been tested as potential anticancer agents and their cytotoxicity properties were evaluated in vitro against HeLa human cervical carcinoma and Jurkat-T acute lymphoblastic leukemia cells. Compounds 2 and 3 are quite cytotoxic for these two cell lines. There is a preferential induction of apoptosis in HeLa cells after treatment with 1-5. However in the case of the more cytotoxic complex (2), cell death is activated due to both apoptosis and necrosis. The interactions of 1-5 with Calf Thymus DNA have been evaluated by Thermal Denaturation methods. All these complexes show no or little (electrostatic) interaction with DNA. The interaction of 2 with two model proteins (cytochrome c and thioredoxin reductase) has been analyzed by spectroscopic methods (vis-UV and fluorescence). Compound 2 manifests a high reactivity toward both proteins. The mechanistic implications of these results are discussed here.

Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

Green barley extract (GB) was investigated for possible anti-cancer activity by examining its anti-proliferative and pro-apoptotic properties on human leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and induced apoptosis, as evidenced by phosphatidylserine (PS) translocation to the outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro-apoptotic effect of GB was found to be independent of mitochondrial depolarization, thus implicating extrinsic cell death pathways to exert its cytotoxicity. Indeed, GB elicited an increase of TNF-α production, caspase-8 and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1 cleavage were strongly inhibited/blocked by the addition of the specific caspase inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling analyses determined that GB treatment enhanced constitutive activation of Lck and Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate that GB induced preferential anti-proliferative and pro-apoptotic signals within B-lineage leukemia/lymphoma cells, as determined by the following biochemical hallmarks of apoptosis: PS externalization, enhanced release of TNF-α, caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our observations reveal that GB has potential as an anti-leukemia/lymphoma agent alone or in combination with standard cancer therapies and thus warrants further evaluation in vivo to support these findings.

Purpose According to the World Health Organization (WHO), breast cancer is the most common cancer affecting women worldwide. In the USA ~12.3 % of all women are expected to be diagnosed with various types of breast cancer, exhibiting varying degrees of therapeutic response rates. Therefore, the identification of novel anti-breast cancer drugs is of paramount importance. Methods The 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore was incorporated into a number of cytotoxins. Three of the resulting dienones, 2a, 2b and 2c, were tested for their antineoplastic potencies in a variety of human breast cancer-derived cell lines, including the triple negative MDA-MB-231 cell line and its metastatic variant, using a live-cell bio-imaging method. Special emphasis was put on dienone 2c, since its anti-cancer activity and its mode of inflicting cell death have so far not been reported. Results We found that all three dienones exhibited potent cytotoxicities towards the breast cancer-derived cell lines tested, whereas significantly lower toxicities were observed towards the non-cancerous human breast cell line MCF-10A. The dienones 2b and 2c exhibited the greatest selective cytotoxicity at submicromolar concentration levels. We found that these two dienones induced phosphatidylserine externalization in MDA-MB-231 cells in a concentration-dependent manner, suggesting that their cytotoxic effect might be mediated by apoptosis. This possibility was confirmed by our observation that the dienone 2c can induce mitochondrial depolarization, caspase-3 activation, cell cycle disruption and DNA fragmentation in MDA-MB-231 cells. Conclusion Our findings indicate that dienone 2c uses the mitochondrial/intrinsic pathway to inflict apoptosis in triple negative MDA-MB-231 breast cancer-derived cells. This observation warrants further assessment of dienone 2c as a potential anti-breast cancer drug.

A series of tri- and bimetallic titanium-gold, titanium-palladium and titanium-platinum derivatives of general formulas [Ti{η5-C5H4(CH2)nPPh2(AuCl)}2].2THF n = 0 (1); n = 2 (2); n = 3 (3) and [TiCl2{η5-C5H4κ-(CH2)nPPh2}2(PtCl2)].2THF (M = Pd, n = 0 (4); n = 2 (5); n = 3 (6); M = Pt, n = 0 (7); n = 2 (8); n = 3 (9)) have been synthesized and characterized by different spectroscopic techniques and mass spectrometry. The molecular structures of compounds 1–9 have been investigated by means of density-functional calculations. The calculated IR spectra of the optimized structures fit well with the experimental IR data obtained for 1–9. The stability of the heterometallic compounds in deuterated solvents (CDCl3, d6-dmso, mixtures 50:50 d6-dmso/D2O, 1:99 d6-dmso/D2O at acidic pH and at neutral pH) has been evaluated by 31P and 1H NMR spectroscopy showing a higher stability for these compounds than for Cp2TiCl2 or precursors [Ti{η5-C5H4(CH2)nPPh2}2]. The new compounds display a lower acidity (1 to 2 units) than Cp2TiCl2. The decomposition products have been identified over time. Complexes 1–9 have been tested as potential anticancer agents and their cytotoxicity properties were evaluated in vitro against HeLa human cervical carcinoma and DU-145 human prostate cancer cells. TiAu2 and TiPd compounds were highly cytotoxic for these two cell lines. The interactions of the compounds with Calf Thymus DNA have been evaluated by Thermal Denaturation (1–9) and by Circular Dichroism (1, 3, 4, 7) spectroscopic methods. All these complexes show a stronger interaction with DNA than that displayed by Cp2TiCl2 at neutral pH. The data is consistent with electrostatic interactions with DNA for TiAu2 compounds and for a covalent binding mode for TiM (M = Pd, Pt) complexes.