ABSTRACT
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Subject(s)
Animals , Humans , Antineoplastic Agents , Pharmacology , Breast Neoplasms , Metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Heterografts , Hypoxia-Inducible Factor 1 , Metabolism , Lignans , Pharmacology , Mice, NudeABSTRACT
Ricin is a plant-derived ribosome-inhibitor which can be easily purified in large quantities from castor beans. It is a potent irreversible inhibitor of protein synthesis. The mode of intoxication could be inhalation, ingestion, intravenous injection.Ricin has been classified as a schedule 1 threat agent by the Chemical Weapons Convention.A fast and sensitive method for the detection of this threat agent is an important tool for preventing or dealing with the consequences of intoxication. An ideal method should be highly sensitve, highly selective, and well capable of identifying ricin in a short assay time. Several methods have been established for ricin detection. This review summaries the development of detection methods for ricin in recent years.