Sulfane sulfur deficiency in malignant cells, increasing the inhibiting action of acetone cyanohydrin in tumor growth

Abstract

PURPOSE: To demonstrate the irreversible poisoning action of the acetone cyanohydrin (AC) in malignant cells. METHODS:Thirty male Swiss mice were inoculated with 1x10³ Ehrlich tumor (ET) cells. The mice were divided into three groups (n=10): CG (saline); ACG1 (1.864 mg/Kg of AC) and ACG2 (2.796 mg/Kg of AC), treated every 48 hours from day 3 until day 13. On day 15 the mice were euthanized and the number of viable cells in ascites was determined. In the meantime, ET cells were incubated with AC (0.5, 1.0, 2.0 μg/mL). Cell viability and percentage of growth inhibition (PGI) were checked after one, two, three, four, 18 and 24 hours. RESULTS:There was reduction in volume and number of viable cells in ACG1 and ACG2 compared to CG. In ACG1 one of the animals did not present ascites. In ACG2 two mice did not present ascites and in CG none of the mice present ascites. The action of AC was dose and time dependent and there was no significant difference among the three doses. CONCLUSION:The acetone cyanohydrin promoted reduction of the tumor and also prevented tumor development in 20% of the treated animals.

Preparation of O-Protected Cyanohydrins by Aerobic Oxidation of α-Substituted Malononitriles in the Presence of Diarylphosphine Oxides

“…Recently, it has been reported that highly functionalized compounds can be prepared from cyanohydrins, and O -acetyl cyanohydrins can also act as a derivatizable directing group for Pd-catalyzed regioselective olefination reactions . Cyanohydrins are also present in a number of natural products, and these compounds show high insecticidal, antiviral, and anticancer activities . Numerous strategies for accessing cyanohydrins or the more stable O-protected derivatives generally rely on highly toxic cyanide sources such as HCN, metal cyanides, and TMSCN. ,,, Until recently, only Ruijter and Orru had documented a Brønsted-acid-catalyzed cyanide-free method, and they utilized trityl isocyanide as a pseudocyanide source to prepare O- trityl cyanohydrin (Scheme ).…”

Histopathological evaluation of tumor necrosis and volume after cyanogenic chemotherapy

“…by the seventh day after inoculation and showed varying shapes and The action of cyanogenic chemotherapy using AC as cyanide source in the experiment developed suggests the ability of tumor cells to irreversibly poison the action of cyanide, thereby providing a dose-and time-dependent effect 12, , as occurred in previous studies 8,9 . Cyanide toxicity occurs in two ways: ATP depletion caused by blockage of oxidative phosphorylation and production of reactive oxygen species 12 .…”

“…This quite possibly occurs by a defect in the detoxification process of cyanide in tumor cells involving cell stocks of sulfur, in which they are easily intoxicated even with low doses of cyanide 8,9 .…”

Sulfane sulfur – new findings on an old topic

“…On the other hand, some aspects of the sulfane sulfur activity were investigated in in vivo studies. Ramalho et al (Ramalho et al, 2013) showed the irreversible poisoning action of the acetone cyanohydrin in Ehrlich tumor cells. The use of acetone cyanohydrin was motivated by the fact that its action in the organism was similar to the molar equivalent of cyanide.…”