ABSTRACT
The spongiolactones are marine natural products with an unusual rearranged spongiane skeleton and a fused ß-lactone ring. These compounds have potential anticancer properties but their mode of action has yet to be explored. Here we employ activity-based protein profiling to identify the targets of a more potent spongiolactone derivative in live cancer cells, and compare these to the targets of a simpler ß-lactone. These hits provide the first insights into the covalent mechanism of action of this natural product class.
Subject(s)
Antineoplastic Agents/pharmacology , Biological Products/pharmacology , Lactones/pharmacology , Leukemia/drug therapy , Leukemia/pathology , Proteomics , Antineoplastic Agents/chemistry , Biological Products/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Jurkat Cells , K562 Cells , Lactones/chemistry , Molecular Structure , Structure-Activity RelationshipABSTRACT
AIMS: To estimate the prevalence of iron deficiency and iron deficiency anaemia using haematological indices. METHODS: Prospective interventional study. Healthy toddlers from Bedouin and Jewish towns in southern Israel. Capillary blood was sampled to assess iron status and nutritional history recorded. Parents were given specific nutritional instructions. Anaemia was defined as haemoglobin level < or = 11 gr/dL. Iron deficiency without anaemia was defined as mean corpuscular volume (MCV) < 70 fL and/or red blood cell width (RDW) > or = 16, with haemoglobin level > 11 gr/dL. Toddlers with iron deficiency were treated with 5 mg/kg/day of elemental iron. Follow-up iron and nutritional status was performed 1 and 2 months after enrolment. RESULTS: At the time of enrolment 42% of the 107 Jewish and 93% of the 43 Bedouin toddlers were iron deficient (p < 0.001). Significantly higher proportions of Bedouin toddlers were breastfed, drank tea, did not eat meat, did not take supplementary iron in their first year of life and were previously diagnosed with anaemia. Rate of follow-up was 55% among Bedouins and 33% among Jews. The mean haemoglobin rise over two months was 0.91 gr/dL (95% CI: 0.63-1.18 gr/dL; p < 0.001) in Bedouins and 0.58 gr/dL (95% CI: 0.14-1.02 gr/dL; p = 0.014) in Jews. CONCLUSIONS: Higher rates of anaemia and iron deficiency, as well as most of the risk factors, found among the Bedouin toddlers, call for the design and implementation of innovative, culturally appropriate interventions in the Bedouin population.
