Abstract
The use of combination drug therapy instead of monotherapy is a new positive and promising approach in the treatment of cancer. Oxidal® and Pyrucet® are food supplements containing Methylene blue (USP), Caffeine (USP), Salicylic acid (USP) and Ethyl Acetoacetate and Ethyl Pyruvate respectively. The therapeutic significance of each of these compounds (their derivatives) is well established, but no data are available on their combined action in in vivo experimental tumor models.
 The aim of the present study was to investigate the in vivo protective effect of mono- and combined experimental therapy with dietary supplements Oxidal® and Pyrucet® in the Graffi myeloid tumor model in hamsters. For this purpose, the two drugs were administered alone or in combination in two treatment regimens - prophylactic (before) and therapeutic (simultaneously) with the transplantation of Graffi tumor cells. The protective effect was determined by the biometric parameters of tumor growth (transplantability, tumor size, mortality, mean survival time, survival rate) recorded during the experiment. The results showed a favorable effect of both drugs, administered alone or in combination, before and simultaneously with the transplantation of tumor cells on the appearance and development of Graffi tumor in hamsters. About 2-fold lower transplantability, prolongation of the latency period by 7 days, inhibition of tumor growth till 30thday of experiments, reduced mortality and increased individual and overall survival time between 7 to 10 days were observed in the Graffi tumor-bearing hamsters with experimental therapy compared to control-Graffi tumor-bearing hamsters, without therapy. The obtained data revealed that Oxidal® and Pyrucet® could be a promising candidate for the treatment of tumor diseases.
Highlights
Cancer is a major health problem associated with an annual increase in morbidity and mortality [1-3]
Transplantabilityi indicates in % the number of hamsters that developed tumors compared to the total number of injected hamsters in the group.On a daily basis following the 7th day after injecting of Graffi tumor cells in the trial animals, via palpation of the skin at the injection site, the appearance of a tumor was reported
For example caffeine works in hepatocellular carcinoma (HCC) cells via activation of MEK/ERK/EGFR signalling pathway [16]; in human gastric cancer cells by activating the caspase-9/caspase-3 signalling pathway [17]; in human breast MCF-7 and MDAMB-231 cancer cell lines by interfering with the cellular metabolism and with lysosomal function [18]; in human colorectal cancer (HT-29 and RKO) lines is linked in part to its antiinflammatory properties [19]
Summary
Cancer is a major health problem associated with an annual increase in morbidity and mortality [1-3]. Despite advances in the early detection of tumors and in the use of chemotherapy, radiation and surgery to treat cancer, there are two main problems with therapy of neoplasms - (multiple) drug resistance and adverse side effects, some of which are lifethreatening or dose-limiting [4]. The search for alternative cancer treatments, as well as the repurposing of conventional drugs to new applications in oncology, is one of the most promising modern strategies to combat cancer. Attention is focused on long-established in clinical practice preparations with a well-known pharmacokinetic/pharmacodynamic profile and toxicity. Oxidal® includes Methylene blue (USP), Caffeine (USP) and Salicylic acid (USP), while Pyrucet® includes Ethyl Acetoacetate and Ethyl Pyruvate. The therapeutic potential of each of these compounds (their derivatives) is well established
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