Modulation of antineoplastic activity of cyclophosphamide by Alstonia scholaris in the Ehrlich ascites carcinoma-bearing mice

Alterations in the neoplastic activity of cyclophosphamide (CPA) by the extract of Alstonia scholaris (ASE) were studied in mice transplanted with Ehrlich ascites carcinoma (EAC). The tumor-bearing animals were injected with various doses of ASE and 25mg/kg of CPA (1/10th of the LD₅₀ dose). The combination of 120mg/kg of ASE with 25mg/kg of CPA was most effective, as it caused the highest tumor regression and enhanced the mean survival time (MST) and the average survival time (AST) up to 42 and 40.7, as against the 29 and 27.5 of CPA alone, respectively. Similarly, when 120mg/kg of ASE was combined with different doses of CPA (3.125 to 50mg/kg), a dose-dependent increase in the anticancer activity was observed up to 25 mg/kg of CPA. However, a further increase in the CPA dose up to 37.5 or 50 mg/kg resulted in toxic side effects and death. The best effect was observed when 120 mg/kg of ASE was combined with 25 mg/kg followed by 12.5 mg/kg of CPA, as evident by the greater tumor remission, when compared with the concurrent doses of either drug alone. The administration of 120 mg/kg of ASE 6 h before the administration of 25 mg/kg of CPA resulted in a drastic decline in the glutathione levels and increased the lipid peroxidation considerably when compared with either drug alone.