Effect of mebendazole on fibrosarcoma in hamsters

Purpose: To investigate the effect of mebendazole on an in vivo solid tumor model of fibrosarcoma in hamsters.Methods: 24 Syrian golden hamsters of both sexes with the approximate body  weight of 100g were randomly distributed in 2 experimental and 2 control groups, with 6 animals in each group. BHK-21/C13 cells (2 x 106) in 1 mL Glasgow Minimum Essential Medium (GMEM) were injected subcutaneously into the back of each animal in 3 groups. The experimental groups were treated with mebendazole  (460 mg/kg) via a gastric tube on a daily basis, immediately after tumor inoculation. In addition, one experimental group received deoxycholic acid 20 mg/kg once a day. After 2 weeks, when the tumors were approximately 1 - 2 cm in the control group, all the animals were sacrificed, and their blood collected for laboratory analysis. The tumors were excised, their weight and diameters measured, and the volumes  calculated. The tumor samples were histopathologically assessed and the main organs toxicologically analyzed. Images were taken and processed by an imaging software, and Ki-67-positive cells in the tumor samples were quantified.Results: Mebendazole diminished tumor mitosis from 18.5 ± 3.02 to 13.5 ± 3.45 (p < 0.05), vasculature and tissue penetration, and increased necroses in tumor  slices. Tumor volume and weight were insignificantly attenuated. Toxicity was not observed.Conclusion: Mebendazole might be an effective non-toxic agent in sarcoma therapy.Keywords: Mebendazole, Hamsters, BHK-21/C13 cells, Fibrosarcoma therapy,  Tumor mitosi

Application of a widely-used tropical anti-worm agent, mebendazole, in modern oncology

Although clinical trials have not been completed, it has already been confirmed that mebendazole, a well-known anti-parasitic drug widely used in the tropical areas, inhibits cancer cell growth. Preclinical studies show that mebendazole notably impedes the growth of malignant and metastatic tumors such as osteosarcoma and soft tissue sarcoma, melanoma, carcinoma (lung, colorectal, breast, ovarian, hepatocellular and adrenocortical), acute myeloid leukaemia, glioblastoma multiforme and  meduloblastoma. Mebendazole can induce the depolymerization of microtubules in neoplasms and newly formed vasculature, stopping tumor growth and neoangiogenesis, along with other proposed mechanisms of action.Keywords: Anthelmintic, Mebendazole, Cancer treatment, Antimicrotubullar effect, Antineoangiogenesi

Influence of the structure of bile acids on their partition coefficient in dibutyl ether and chloroform

Bile acids are well known natural surfactants able to modify the per­meability of biological membranes. The logarithm of partition coefficient between, tradi­tionally used, n-octanol and water is a measure of lipophilicity as a predictor of solute membrane partitioning. The aim of this work was to determine partition coefficients of bile acids in a mixture of water and chloroform and dibutyl ether at different pH values and with addition of different concentrations of sodium ions, and to examine the influence of the structure of bile acid nucleus on measured partition coefficients. Partition coefficients of three bile acid salts were determined using shake-flask method and the concentration of bile acids was determined after twelve hours of shaking at the room temperature in aqueous and organic layer using reversed phase HPLC with DAD detector on 210 nm. For all three analysed bile acid salts values of logP are lower in dibutyl ether than in chloroform. At certain pH values, curves representing the dependence of partition coeffi­cient on pH value intersect, and these are the pH values for which partition coefficients are the same for both solvents. Increasing the solution ionic strength, this intersection is shifted toward lower pH values. It is found that, for both organic solvents, after the addition of hy­droxyl group in the steroid nucleus (i.e. if the bile acid is less hydrophobic) the value of logP falls, especially if more hydroxyl groups are present. With chloroform as a solvent, system quickly comes to excess with electrolyte ions than with dibutyl ether. [Projekat Ministarstva nauke Republike Srbije, br. 172021