BackgroundIL-1β is a pleiotropic pro-inflammatory cytokine and its up-regulation is closely associated with various cancers including gastrointestinal tumors. However, it remains unclear how IL-1β may contribute to the initiation and development of these inflammation-associated cancers. Here we investigated the role of IL-1β in colon cancer stem cell (CSC) development.MethodsUsing self-renewal assay, soft-agar assay, invasion assay, real-time PCR analysis, immunoblot assay and shRNA knockdown, we determined the effects of IL-1β on cancer stem cell development and epithelial-mesenchymal transition (EMT) in human primary colon cancer cells and colon cancer cell line HCT-116.ResultsWe found that IL-1β can increase sphere-forming capability of colon cancer cells in serum-free medium. IL-1β-induced spheres displayed an up-regulation of stemness factor genes (Bmi1 and Nestin) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activator Zeb1 was increased in IL-1β-induced spheres, indicating that there might be a close association between EMT and IL-1β-induced CSC self-renewal. Indeed, IL-1β treatment led to EMT of colon cancer cells with loss of E-cadherin, up-regulation of Zeb1, and gain of the mesenchymal phenotype. Furthermore, shRNA-mediated knockdown of Zeb1 in HCT-116 cells reversed IL-1β-induced EMT and stem cell formation.ConclusionOur findings indicate that IL-1β may promote colon tumor growth and invasion through activation of CSC self-renewal and EMT, and Zeb1 plays a critical role in these two processes. Thus, IL-1β and Zeb1 might be new therapeutic targets against colon cancer stem cells.

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Many compounds containing a five-membered heterocyclic ring display exceptional chemical properties and versatile biological activities. In this Minireview, thiadiazoles are summarized according to their therapeutic potential, highlighting the versatility of this scaffold in medicinal chemistry. The unique properties of thiadiazoles are also discussed in relation to their potential effect on activity. Thiadiazole is a bioisostere of pyrimidine and oxadiazole, and given the prevalence of pyrimidine in nature it is unsurprising that thiadiazoles exhibit significant therapeutic potential. The sulfur atom of the thiadiazole imparts improved liposolubility, and the mesoionic nature of thiadiazoles makes these compounds better able to cross cellular membranes. By summarizing the thiadiazole-containing compounds reported in recent decades, we aim to give a brief introduction to their synthesis and diverse biological activities, such as anti-inflammatory, anticancer, antibacterial, antifungal, antiviral, antiparasitic, anticonvulsant, anticoagulant, antidiabetic, and to show the significant utility of the thiadiazole scaffolds in medicinal chemistry.

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