Betulin-3,28-diphosphate as a Component of Combination Cytostatic Drugs for the Treatment of Ehrlich Ascites Carcinoma In Vitro and In Vivo Experiments

Abstract

The activity of betulin-3,28-diphosphate (BDP) in combination with the cytostatics such as 5-fluorouracil (5-FU) and hydrazine sulfate (HS) was demonstrated by using the transplanted Ehrlich ascites carcinoma (EAC) in mice. The dose-dependent effect of combination drugs BDP + HS and BDP + 5-FU was revealed by in vitro experiments on rats. The synergetic effect of HS and BDP on oxidative stress and energy metabolism was established. The malonic dialdehyde (MDA) level both in plasma and erythrocytes decreased by 87 ± 2%, and the superoxide dismutase (SOD) activity increased by 105 ± 7% in comparison with the control. The combination of BDP + HS promoted the increase of lactate dehydrogenase (LDH) activity in the reverse reaction by 195 ± 21% compared to the control. The combination drug of 5-FU with BDP caused the synergetic decrease of the lipid peroxidation (LPO) intensity estimated by the MDA level decrease up to 14 ± 4% compared to pure compounds. Betulin-3,28-diphosphate in combination with cytostatics for EAC treatment improved the animal health status, as well as decreased the cytostatics dose that can be used in palliative therapy.

The Implication of a Novel Herbal Formulation in Reversal of Drug-Resistance for Cancer Treatment

“…In this study, we observed 2 fold decrease in free radicals when treated with SR033 as compared to untreated controls, however, 1.2 fold decrease was observed when compared 5FU alone groups with SR033 + 5FU groups. The effect of SR033 in combination to 5FU showed comparable results to abovementioned reports (56,57). While the data does show that SR033 alone significantly reduces the number of free radicals, the practical application of using SR033 alone to treat cancer is not feasible (58).Similar studies were also performed earlier (59,60).…”

“…Treatment of HeLa-R cells at IC50 values of HeLa cells in the combination of SR033 (600 μg/mL) with 5FU (2 μg/mL) and PTX (5.96×10 -3 μg/mL) resulted in 80% and 88% death of HeLa-R, treated with SR033 + 5FU, hence displaying its antioxidant capability. However, in earlier reports, use of 5FU with Irinotecan resulted in a 3 fold decrease in free radicals (56), whereas no significant increase was observed withbetulin-3, 28-diphosphate (57). In this study, we observed 2 fold decrease in free radicals when treated with SR033 as compared to untreated controls, however, 1.2 fold decrease was observed when compared 5FU alone groups with SR033 + 5FU groups.…”

“…Nowadays, application of herbal compounds as complementary and alternative medicine/ adjuvants is increasing to overcome chemo-toxicity and resistance. Thus, the combinatorial approach with herbal compounds can be adopted to reduce the toxic effects of chemotherapy as well as combating drug resistance (50)(51)(52)(53)(54)(56)(57)(58)(59)(60). In the present study, we have tested a poly-herbal formulation, SR033in combination with 5FU to reduce toxicity, to increase its efficiency and to prevent oxidative damage.…”

The Improvement of Betulin-3, 28-Diphosphate Water-Solubility by Complexation With Amines–meglumine and Xymedon

“…In addition to improved solubility, betulin phosphates and phosphonates showed high activity as potential drugs [18][19][20][21][22][23]. In vitro and in vivo experiments demonstrated antimicrobial [19], antifungal [20], anti-inflammatory, antiviral [21] activities and an antitumor effect in the treatment of ductal carcinoma, glioblastoma, melanoma [22], Ehrlich ascites carcinoma [23] and other diseases.…”

Antioxidant, Metabolic and Antitumor Activity of Triterpenoids Combination With Cytostatics

“…Triterpenoids are able to potentiate the 5-fluorouracil effect by affecting different stages of esophageal carcinoma and other tumors [8,9]. Previously, we showed the animals state improvement indicated by survival, body weight, wool, behavior, reduced cardiotoxicity when Ehrlich carcinoma was treated by the combination of 5-fluorouracil or hydrazine sulfate with betulin-3,28-diphosphate in in vivo experiment [10]. The effect may be due to the decreased dose of high toxic cytostatics and increased metabolic processes in an animal body, including antioxidant enzyme protection and energy metabolism activation.…”