The effects of cyclophosphamide alone and in combination with ascorbic acid against murine ascites Dalton's lymphoma

Objective : To evaluate the therapeutic activity of cyclophosphamide alone and in combination with ascorbic acid against murine ascites Dalton′s lymphoma.
Materials and Methods: Cyclophosphamide (CP) is an anticancer drug with immunosuppressive activity, while ascorbic acid (AA) is an antioxidant. Ascites Dalton′s lymphoma (DL) was maintained by intraperitoneal (i.p.) transplantation of tumor cells in Swiss albino mice. Tumor transplanted mice were divided into four groups. Group-I mice received normal saline only and served as control. Group-II mice were given 1% ascorbic acid through drinking water from the 5th to the 10th day. Group-III mice were injected i.p. with a single dose of CP (200 mg/kg) on the 10th day of tumor transplantation. Group IV mice received 1% ascorbic acid from the 5th day onwards and, then, a single dose of CP, i.p., on the 10th day of tumor transplantation. In groups III and IV, after 24, 48, 72, and 96 h of CP treatment the liver, kidneys, spleen, and tumor tissue were collected for biochemical determinations. In group II, which received AA only from the 5th to the 10th day, the same tissues were collected on the 10th day of tumor transplantation. The changes in reduced glutathione (GSH) and carbohydrate in tumor cells as well as the liver, kidney, and spleen of tumor-bearing mice in relation to the antitumor activity of CP alone or in combination with AA were evaluated. The quantitative changes in sialic acid level of DL cells under these treatment conditions were also determined.
Results: AA and CP combination in tumor-bearing mice was found to be more effective against DL as it caused a 257% increase in life span compared with control, while it was 106% with AA and 188% with CP alone (ANOVA, P ≤ 0.001). The reduced glutathione (GSH) level increased in DL cells with tumor growth. Compared with CP alone, the combination treatment (AA + CP) resulted in a more pronounced effect causing decreases in non-protein thiol (NPSH) as well as sialic acid levels in DL cells (ANOVA, P≤ 0.001).
Conclusion: The drug-mediated lowering of GSH levels in DL cells may be involved in the cytotoxicity due to CP (group-III) as well as AA + CP combination (group-IV). An overall decrease in the sialic acid content of DL cells after combination treatment may also play a role to bring about alterations in the tumor cells, cell-cell interaction and enhanced tumor regression.