Anti-cancer Properties of Anphen Sodim and Its Effect on Antiapoptotic Proteins of the Bcl-2 Family

Abstract

Aims: It’s known that apoptosis, necessary for renewal and vital activity of cells, is suppressed in the tumour cell. The strategies of anti-cancer therapy may be a search of the new drugs and development of targeted substances, including the Bcl-2 family proteins, to initiate apoptosis. One of such drugs may be spatially substituted phenol anphen sodium (AS), a derivative of dibunol that can inhibit free radical oxidation and interact with peroxide radicals in the cell, and has also biological activity. The study aims to investigate possible anti-cancer, antioxidant AS action on experimental tumours of the ascitic sarcoma 37 and Lewis carcinoma of F1 (C57Bl × DBA) mice. The influence of AS drug on Bcl-2 family proteins level in blood plasma Lewis carcinoma cells suspension in spleen cells of white mice was determined.   Place and Duration of Investigation: Emanual Institute of Biochemical Physics Russian Academy of Sciences, Moscow, Russia, between October 2013 and March 2018. Metodology: To examine AS anti-cancer properties, the kinetic curves of tumour development and the number of ascitic cells in ascitic fluid were studied; the changes in anti-apoptotic Bcl-2 proteins and Bcl-2 family proteins levels were monitored by immunoblotting. Results: A significant (100%) anti-tumour effect of the antioxidant sodium antepoxide AS (2- (carboxy) -2- (N-acetylamino) -3- (3 ', 5'-di-t-butyl-4'-hydroxyphenyl) - sodium propionate was seen when it was administered to mice after transplantation of ascites sarcoma cells 37. The reduction of the Bcl-2 protein took place in the blood plasma of F1 mice (C57B1 × DBA), when AS (10-4M) was administered to mice before transplantation by Lewis cells of carcinoma, as shown by immunoblotting. At the same time, this did not change the survival rate of mice. The administration of AS into the Lewis carcinoma cell suspension causes a dramatic decrease in the amount of monomer and homodimer of Bcl-2 protein for 1-3 hours in these cells. AS drug administered during 4 days (10-4 M) to white mice caused a change in the ratio of Bcl-2 family proteins in the spleen cells, indicating the onset of the mitochondrial pathway of apoptosis. Conclusion: The anti-cancer effect of AS can be associated with an effect on the molecular targets of the  apoptosis pathway, including the proteins of the Bcl-2 family.