The present article demonstrates selective cytotoxicity against cancer cells of the complexes [Co(LD)2]I2∙CH3OH (1), [CoLD(NCS)2] (2) and [VOLD(NCS)2]∙C6H5CH3 (3) containing the dipodal tridentate ligand LD = N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine), formed in situ. All tested complexes expressed greater anticancer activities and were less toxic towards noncancerous cells than cisplatin. Cobalt complexes (1 and 2) combined high cytotoxicity with selectivity towards cancer cells and caused massive tumour cell death. The vanadium complex (3) induced apoptosis specifically in cancer cells and targeted proteins, controlling their invasive and metastatic properties. The presented experimental data and computational prediction of drug ability of coordination compounds may be helpful for designing novel and less toxic metal-based anticancer species with high specificities towards tumour cells.

IntroductionThe standard therapy for exocrine pancreatic insufficiency (EPI) is porcine-derived pancreatic enzyme replacement therapy (PERT). In the present study we tested a new approach with a mixture of pancreatic-like enzymes of microbial origin (PLEM) in a 1-week efficacy study in EPI pigs. In addition to the conventionally used coefficient of fat and nitrogen absorption (CFA and CNA), parameters that more accurately reflect the nutritional and health status, such as changes in the lipemic index (LI), plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels, and somatic growth, were determined.Material and methodsA PLEM dose containing 120 000 active lipase units, 80 000 active protease units and 12 000 active amylase units (all from Sigma, St. Louis, MO) was given as a powder, twice daily with a meal (40 g fat/meal) to 8 EPI pigs for 7 days. Ten healthy pigs were used as a comparator.ResultsThe PLEM enhanced fat and protein digestion, and reversed growth impairment in EPI pigs. With treatment, CFA and CNA increased by 59% and 43% (p < 0.05), respectively. Although fat and protein absorption were lower than in the comparator, the postprandial blood lipid profile was normal as in healthy pigs. The mucosal thickness significantly increased by 27%, 50% and 26%, in the proximal, middle, and distal jejunum (p < 0.05) with treatment and resembled that of healthy animals.ConclusionsPancreatic-like enzymes of microbial origin supported somatic growth and normalized the postprandial lipid profile. As a measure of efficacy, postprandial LI, TG and NEFA are viable endpoints to be explored in human trials.

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