Blume Essential Oil Inhibits Metastatic Melanoma Cell Proliferation by Triggering an Incomplete Tumour Cell Stress Response.

Given the known pro-oxidant status of tumour cells, the development of anti-proliferative strategies focuses on products with both anti- and pro-oxidant properties that can enhance antitumour drug cytotoxicity. We used a essential oil (CINN-EO) and assessed its effect on a human metastatic melanoma cell line (M14). Human PBMCs and MDMs from healthy donors were used as normal control cells.

Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine.

Background: For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action.

Schistosomiasis control: praziquantel forever?

Since no vaccine exists against schistosomiasis and the molluscs acting as intermediate hosts are not easy to attack, chemotherapy is the main approach for schistosomiasis control. Praziquantel is currently the only available antischistosomal drug and it is distributed mainly through mass administration programs to millions of people every year. A number of positive features make praziquantel an excellent drug, especially with regard to safety, efficacy, cost and ease of distribution.

Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites.

Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites.

Microrna-221 and microrna-222 modulate differentiation and maturation of skeletal muscle cells.

Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs that have recently emerged as important regulators of gene expression. They negatively regulate gene expression post-transcriptionally by translational repression and target mRNA degradation. miRNAs have been shown to play crucial roles in muscle development and in regulation of muscle cell proliferation and differentiation.

Genetic analysis of decreased praziquantel sensitivity in a laboratory strain of Schistosoma mansoni.

A laboratory strain of Schistosoma mansoni subjected to repeated in vivo praziquantel (PZQ) treatments for several generations has been previously found to have lesser sensitivity to the drug than the original unselected strain. In this study we have collected evidence on the mode of inheritance of the partial insensitivity exhibited by the PZQ-selected schistosomes. A single male and a single female worm of the two strains, assorted in the four possible combinations, were introduced into the mesenteric veins of mice and the eggs produced by each pair were used as the source of the F(1) progeny.

Schistosoma mansoni: lack of correlation between praziquantel-induced intra-worm calcium influx and parasite death.

The schistosomicidal activity of praziquantel (PZQ) is accompanied by a large influx of calcium into the worms, suggesting that this phenomenon could be the source of the observed muscular contraction, surface disruption and eventual death of the parasite. We have incubated live adult schistosomes in a medium containing radioactive calcium and we were able to confirm that PZQ does indeed stimulate calcium entry into the parasite. An even higher calcium uptake, however, occurred in schistosomes exposed to PZQ after pre-incubation with cytochalasin D, a condition that suppresses PZQ schistosomicidal effects and allows the complete survival of the parasites.

Cytochalasin D abolishes the schistosomicidal activity of praziquantel.

To test the hypothesis that calcium channels of schistosomes are the targets for the action of praziquantel, we subjected schistosomes in vitro to pharmacological agents capable of interfering with the functioning of calcium channels. After 1-h exposure to these agents, praziquantel was added and incubation continued overnight. Worms were then washed, resuspended in drug-free medium and observed during the following 7-10 days.