Negative Impact of Total Body Irradiation on the Antitumor Activity of Rhenium-(I)-diselenoether.

It has been shown that a rhenium-(I)-diselenoether complex had significant antitumor activity in MDA-MB231 tumor-bearing mice after repeated oral or intraperitoneal administrations for 4 weeks at safe doses of 10 mg/kg/day. It has also been suggested that lower doses could be as effective as this dose. We, thus, tested two doses (5 and 10 mg/kg). The drug was orally administered daily by gavage for 4 weeks and for a further 2 weeks with or without 15 mg/kg paclitaxel treatment (intravenously, once a week). This experiment was performed in MDA-MB 231 tumor-bearing mice, as a model of resistant breast tumor. However, in contrast to previous studies, the mice were pretreated with total body irradiation to increase the tumor growth. These two doses were safe, even in combination with paclitaxel. The expected tumor regression was not observed with the rhenium-(I)-diselenoether complex, and there was even a significant increase of the tumor volume in mice treated with 10 mg/kg versus controls. No synergism was observed with paclitaxel. We comment on the possible negative impact of radiotherapy on the antitumor activity of the drug. Plasma and tumor rhenium and selenium concentrations are also reported.

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations.

Rhenium (I)-diselenoether has shown promising antiproliferative efficacy in both in vitro and in vivo models. However, the maximal tolerated dose and dose-effect relationships have not been fully addressed for this compound. Here, we evaluated the tolerance and efficacy of three dose-levels (namely 10, 40 and 100 mg/kg) intraperitoneally administered daily over 28 days in mice bearing the resistant MDA-MB231 breast cancer cell line. The upper dose was found to be toxic and was reduced to 60 mg/kg. The 10 mg/kg dose well tolerated, whereas 40 mg/kg was associated with 10% mortality (LD10). Both 10 and 40 mg/kg dosing achieved a significantly similar regression of tumor growth compared with untreated animals. This study suggests that 10 mg/kg daily is the recommended dose for rhenium (I) diselenoether.

Influence of Cultivation Parameters on the Mineral Composition of Kiwi Fruit from Corsica.

The effect of four cultivation parameters (postmaturity harvest date, storage period at 0 °C, and input of nitrogen and potassium fertilizers) on the mineral composition of kiwi fruit (Actinidia deliciosa var. Hayward) from Corsica were evaluated. The kiwi fruit were harvested on three dates at two-week intervals and some fruit were stored for three and four months. The kiwi fruit orchard was fertilized with controlled levels of nitrogen (five levels) and potassium (three levels) during one growing season. The concentrations of 67 elements in kiwi fruit were measured using various analytical methods, such as flow injection spectrophotometry, flame atomic absorption spectrometry, flame atomic emission spectrometry, electrothermal atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry, inductively coupled plasma mass spectrometry, and filtration. The main elements in kiwi fruit are K, N, Cl, P, and Si and, to a lesser amount, Ca, Mg, Na, and Fe. This study demonstrates a high degree of difference in the amount of 23 mineral elements depending on the harvest date, the time of storage, and the input of fertilizers.

Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer.

Rhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex. The Re-diselenoether showed a potent inhibitory effect on MDA-MB231 cell division in vitro, which lasted when the complex was no longer present in the culture. Re-diselenoether induced a remarkable reduction of the volume of the primitive breast tumors and of the pulmonary metastases without clinical signs of toxicity, in mice-bearing a MDA-MB231 Luc+ tumor, orthotopically transplanted, after a daily oral administration at the dose of 10 mg/kg/d. Interestingly, an antagonism was observed when cisplatin was administered as a single i.p. injection 1 week after the end of the Re-diselenoether administration. In an effort to gain insight of the mechanisms of action of Re-diselenoether complex, interaction with 9-methylguanine as a nucleic acid base model was studied. We have shown that Re-diselenoether gave both mono- and bis-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.

Uptake and efflux of rhenium in cells exposed to rhenium diseleno-ether and tissue distribution of rhenium and selenium after rhenium diseleno-ether treatment in mice.

UNLABELLED: We proposed a new water-soluble rhenium diseleno-ether compound (with one atom of Re and two atoms of Se) and investigated the uptake of Re into the nucleus of malignant cells in culture exposed to the compound for 48 h and its efflux from the nucleus after a post-exposure period of 48 h, as DNA is the main target of Re. We also studied the distribution of both Re and Se in the main organs after an oral administration of 10 or 40 mg/kg Re diseleno-ether to mice for four weeks, five days-a-week. MATERIALS AND METHODS: Re and Se concentrations were assayed by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using the Wilcoxon signed-rank test, comparing two related groups. RESULTS: We observed that Re was well incorporated into the nucleus of malignant cells in the most sensitive cells MCF-7, derived from human breast cancer, and that there was no efflux of Re. In contrast, in MCF-7 resistant cells (MCF-7 Mdr and MCF-7 R), A549 and HeLa cells, there was significant efflux of Re from the nucleus after the wash-out period. In mice, an important and dose-dependent uptake of both Re and Se was observed in the liver, with lower concentrations in kidneys. The lowest concentrations were observed in blood, lung, spleen and bones. There was a significant increase of Re concentrations in the blood, liver and kidney in mice treated with Re diseleno-ether at the dose of 40 mg/kg/24 h versus those treated at the dose of 10 mg/kg/24 h. There was a significant increase of Se concentrations in all tissues with the dose of Re diseleno-ether of 10 mg/kg/24 h versus controls, and a significant increase in the liver in mice treated with dose of Re diseleno-ether of 40 mg/kg/24h versus those treated with 10 mg/kg/24 h. CONCLUSION: We are the first to demonstrate that a compound combining Re and Se in a single molecule, is able to deliver Re and Se to the organism via an oral route, for cancer treatment.

Relationships between the leaf and fruit mineral compositions of Actinidia deliciosa var. Hayward according to nitrogen and potassium fertilization.

The variations of the elements that are examined most frequently during foliar analysis were determined for kiwi as a function of different nitrogen and potassium fertilizer loads. The values recorded demonstrated the existence of a relation between the leaves and the fruit. Two groups of elements were identified that exhibited different responses. The first group comprised elements that, in leaves and fruits, presented a different evolution as a function of at least one of the fertilizers. This group included B, Cu, Fe, Na, and Zn. The second group comprised elements that, in both leaves and fruits, exhibited a comparable evolution as a function of both fertilizer types. This group included N, Ca, Mg, Mn, P, and K.

Influence of cultivation parameters on the composition of volatile compounds and physico-chemical characteristics of kiwi fruit.

BACKGROUND: The effect of four cultivation parameters (post-maturity harvest date, storage period at 0 °C and input of nitrogen or potassium fertilisers) on the physico-chemical characteristics and composition of volatile compounds in kiwi fruit (Actinidia deliciosa) were evaluated. Five physico-chemical parameters were selected, namely, pH, total acidity, dry matter, conductivity and refractive index. To our knowledge, no published data are available concerning the influence of nitrogen or potassium fertilisers on the volatile compounds and physico-chemical parameters in kiwi fruit. RESULTS: Except for total acidity, these parameters were only weakly influenced by cultivation parameters. The concentrations of five main volatile compounds [hexanal, (E)-hex-2-enal, hexan-2-ol, ethyl butyrate and hexanol] were also measured using gas chromatography and gas chromatography-mass spectrometry. This work showed that the total content of volatile compounds decreased with post-maturity harvest date and storage period of 3 months. In contrast, the input levels of nitrogen and potassium had little effect on the concentrations of volatile components CONCLUSION: This study demonstrates a high degree of difference in the physiochemical parameters and volatile composition of kiwi fruit, depending on the harvest date, the time of storage and the input of fertilisers.

Partitioning the relative contributions of inorganic plant composition and soil characteristics to the quality of Helichrysum italicum subsp. italicum (Roth) G. Don fil. essential oil.

Composition of Helichrysum italicum subsp. italicum essential oil showed chemical variability according to vegetation cycle, environment, and geographic origins. In the present work, 48 individuals of this plant at different development stages and the corresponding root soils were sampled: i) 28 volatile components were identified and measured in essential oil by using GC and GC/MS; ii) ten elements from plants and soils have been estimated using colorimetry in continuous flux, flame atomic absorption spectrometry, or emission spectrometry (FAAS/FAES); iii) texture and acidity (real and potential) of soil samples were also reported. Relationships between the essential-oil composition, the inorganic plant composition, and the soil characteristics (inorganic composition, texture, and acidity) have been established using multivariate analysis such as Principal Component Analysis (PCA) and partial Redundancy Analysis (RDA). This study demonstrates a high level of intraspecific differences in oil composition due to environmental factors and, more particularly, soil characteristics.