Vitamin B12b Enhances the Cytotoxicity of Diethyldithiocarbamate in a Synergistic Manner, Inducing the Paraptosis-Like Death of Human Larynx Carcinoma Cells

We have shown that hydroxycobalamin (vitamin B12b) increases the toxicity of diethyldithiocarbamate (DDC) to tumor cells by catalyzing the formation of disulfiram (DSF) oxi-derivatives. The purpose of this study was to elucidate the mechanism of tumor cell death induced by the combination DDC + B12b. It was found that cell death induced by DDC + B12b differed from apoptosis, autophagy, and necrosis. During the initiation of cell death, numerous vacuoles formed from ER cisterns in the cytoplasm, and cell death was partially suppressed by the inhibitors of protein synthesis and folding, the IP3 receptor inhibitor as well as by thiols. At this time, a short-term rise in the expression of ER-stress markers BiP and PERK with a steady increase in the expression of CHOP were detected. After the vacuolization of the cytoplasm, functional disorders of mitochondria and an increase in the generation of superoxide anion in them occurred. Taken together, the results obtained indicate that DDC and B12b used in combination exert a synergistic toxic effect on tumor cells by causing severe ER stress, extensive ER vacuolization, and inhibition of apoptosis, which ultimately leads to the induction of paraptosis-like cell death.

Effect of vitamin B12b injections on the growth of young Merino sheep

In two experiments near Robe in the south-east of South Australia, on soil highly prone to the occurrence of cobalt deficiency in sheep, the effect of injections of vitamin B12b (hydroxocobalamin) on grossly cobalt-deficient weaner sheep and suckling lambs was compared with the effect of oral doses of cobalt as liquid drenches or ruminal pellets. All the supplements used were effective in treating cobalt-deficient weaned sheep or preventing the onset of cobalt deficiency in lambs. A single injection of vitamin B12b (1 mg), under the conditions of these experiments, satisfied the requirements of lambs for 14 weeks and cobalt-deficient weaner sheep for up to 40 weeks. The use of vitamin B12b in preventing or correcting cobalt deficiency in sheep in the field is discussed. Serum vitamin B12b concentration was not a reliable indicator of the vitamin B12b status of young sheep which had been given single injections of vitamin B12b. Vitamin B12b, deficiency in sheep was associated withdecreased concentrations of blood haemoglobin and of glucose, total proteins, urea and cholesterol in blood serum. The activities of serum aspartate transminase and alkaline phosphatase did not appear to be affected by the vitamin B12b status of the sheep.