Synthesis and tumour cell uptake studies of gadolinium(III)–phosphonium complexes

The synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported. Their lipophilicity and uptake in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines are presented. The in vitro cytotoxicity of all complexes was determined to be low at therapeutically-relevant concentrations. Selected Gd(III) complexes are potential candidates for further investigation as theranostic agents.

Cerebrospinal fluid of chronic osteoarthritic patients induced interleukin-6 release in human glial cell-line T98G

Background Chronic osteoarthritic pain is not well understood in terms of its pathophysiological mechanism. Activated glial cells are thought to play a role in the maintenance of chronic pain. T98G glioblastoma cell line was previously observed to release higher amounts of interleukin-6 (IL-6) when treated with cerebrospinal fluid (CSF) from patients with another chronic pain condition, post-herpetic neuralgia. In this study, we investigated the ability of CSF from patients diagnosed with knee osteoarthritis suffering from chronic pain, to trigger the release of pro-inflammatory cytokines, IL-6, IL-1beta and tumour necrosis factor alpha (TNF-α) from T98G. Characterization of upstream signalling was also explored. Methods 15 osteoarthritis patients undergoing total knee replacement due to chronic knee pain and 15 patients without pain undergoing other surgeries with spinal anaesthesia were prospectively recruited. CSF was collected during anaesthesia. CSF were added to cultured T98G cells in the presence of lipopolysaccharide. IL-6, IL-1β and TNF-α release from T98G cells were measured using enzyme immunoassay. Antibody array and western blotting were performed using CSF-triggered T98G cell lysates to identify possible signalling targets. Age, gender and pain scores were recorded. Mann-Whitney U test was used to compare IL-6 release and protein expression between groups. Association between IL-6 and pain score was analysed using linear regression. Results Significant higher levels of IL-6 were released by T98G cells when induced by osteoarthritis patients' CSF in presence of lipopolysaccharide. IL-6 levels showed positive association with pain score (adjusted B estimate= 10.1 (95% Confidence Interval 4.3-15.9); p= 0.001). Antibody array conducted with 6 pooled T98G cell lysate induced with osteoarthritis pain patient CSF identified greater than 2-fold proteins including STE20-related kinase adaptor protein and spleen tyrosine kinase. Further validation done using western blotting of individual CSF-triggered T98G cell lysate showed non-significant increase. Conclusion Higher IL-6 release from T98G when triggered by OA CSF, in the presence of lipopolysaccharide, suggest presence of "unknown molecule" in CSF that may be crucial in the maintenance phase of chronic pain in our osteoarthritis population. Further studies on the signalling pathways involved in pain and relevance of IL-6 release from T98G in other pain models are needed.

Essential Oil from Arnica Montana L. Achenes: Chemical Characteristics and Anticancer Activity

Mountain arnica Arnica montana L. is a source of several metabolite classes with diverse biological activities. The chemical composition of essential oil and its major volatile components in arnica may vary depending on the geographical region, environmental factors, and plant organ. The objective of this study was to characterize the chemical composition of essential oil derived from A. montana achenes and to investigate its effect on induction of apoptosis and autophagy in human anaplastic astrocytoma MOGGCCM and glioblastoma multiforme T98G cell lines. The chemical composition of essential oil extracted from the achenes was examined with the use of Gas Chromatography–Mass Spectrometry GC-MS. Only 16 components of the essential oil obtained from the achenes of 3-year-old plants and 18 components in the essential oil obtained from the achenes of 4-year-old plants constituted ca. 94.14% and 96.38% of the total EO content, respectively. The main components in the EO from the arnica achenes were 2,5-dimethoxy-p-cymene (39.54 and 44.65%), cumene (13.24 and 10.71%), thymol methyl ether (8.66 and 8.63%), 2,6-diisopropylanisole (8.55 and 8.41%), decanal (7.31 and 6.28%), and 1,2,2,3-tetramethylcyclopent-3-enol (4.33 and 2.94%) in the 3- and 4-year-old plants, respectively. The essential oils were found to exert an anticancer effect by induction of cell death in anaplastic astrocytoma and glioblastoma multiforme cells. The induction of apoptosis at a level of 25.7–32.7% facilitates the use of this secondary metabolite in further studies focused on the development of glioma therapy in the future. Probably, this component plays a key role in the anticancer activity against the MOGGCCM and T98G cell lines. The present study is the first report on the composition and anticancer activities of essential oil from A. montana achenes, and further studies are required to explore its potential for future medicinal purposes.

ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES AGAINST MORPHINE: PRODUCTION, PROPERTIES AND PROSPECTS OF USE

This paper describes a technique for producing anti-idiotypic monoclonal antibodies (Ab2) against two morphine derivatives. The specificity of the obtained antibodies was investigated using enzyme immunoassay. The biological activity of the antibodies was studied using an in-vitro model of human glioblastoma T98G cell line prolifer ation.