Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer.

PURPOSE: In the present study, we screened a compound library containing 1,600 clinically used compounds with the aim to identify compounds, which potentially could be repositioned for colon cancer therapy. METHODS: Two established colon cancer cell lines were tested using the fluorometric microculture cytotoxicity assay (FMCA). For compound comparison connectivity map (CMAP) analysis, NCI 60 data mining and protein kinase binding measurements were performed. RESULTS: Sixty-eight compounds were defined as hits with activity in both of these cell lines (<40 % cell survival compared with control) at 10 µM drug concentration. Analysis of chemical similarity of the hit compounds revealed several distinct clusters, among them the antiparasitic benzimidazole group. Two of these compounds, mebendazole (MBZ) and albendazole (ABZ) are registered for human use. Data from the NCI 60 cell line panel revealed only modest correlation between MBZ and ABZ, indicating differences in mechanism of action. This was further supported when gene expression signatures were compared in the CMAP database; ABZ ranked very low when MBZ was used as the query signature. Furthermore, MBZ, but not ABZ, was found to significantly interact with several protein kinases including BCR-ABL and BRAF. Analysis of the diagnosis-specific activity of MBZ showed activity in 80 % of the colon cancer cell lines in the NCI 60 panel. Three additional colon cancer cell lines and three cell models with non-malignant phenotypes were subsequently tested, confirming selective colon cancer activity of MBZ. CONCLUSION: MBZ seemingly has repositioning potential for colorectal cancer therapy.

Non-animal stabilized hyaluronic acid: a new formulation for the treatment of osteoarthritis.

Hyaluronic acid (HA) is a major component of human synovial fluid, providing the rheologic properties (elasticity and viscosity) that enable the synovial fluid to perform lubricating and shock-absorbing functions within the healthy joint. Over the last 2 decades, HA preparations have become established in intra-articular therapy of osteoarthritis (OA), particularly OA of the knee. Existing HA preparations, both cross-linked and non-cross-linked, are all administered by courses of multiple injections, and all have been associated with variable success rates. The clinical profile of an HA preparation is inextricably linked to the product's physicochemical properties. For example, the molecular structure of the HA affects the intra-articular residence time, which should in turn influence the duration of action post-injection. Non-animal stabilized hyaluronic acid (NASHA) is a new-generation HA preparation, produced wholly from non-animal sources. NASHA is stabilized using a carefully controlled cross-linking process, which increases the intra-articular residence time from hours to weeks. This facilitates single-injection treatment for OA without affecting the biocompatibility of HA. This review evaluates the properties of NASHA, including the available clinical data, in the context of previously developed HA preparations.