ABSTRACT
Total five plants, three from Mizoram (Dillenia pentagyna, Ageratum conyzoides, Blumea lanceolaria) and two from Meghalaya (Potentilla fulgens, Taxus baccata) were studied for their antitumour activity against murine ascites Dalton's lymphoma (DL) in vivo. Only three plants showed the different magnitude of antitumour activity. Out of these three plants, the antitumour activity was maximally observed with the methanol extract of the stem bark of D. pentagyna as compared to the aqueous extract of the roots of A. conyzoides and aqueous extract of the root of P. fulgens. An increase in glutathione levels in Dalton's lymphoma cells was observed during tumour growth. Changes in glutathione and protein levels were also investigated in the liver and Dalton's lymphoma cells of tumour-bearing mice following the treatment with the extract of D. pentagyna which showed the highest antitumour activity as compared to the other two plant extracts. Glutathione in the liver and DL cells of treated tumour-bearing mice was found to be decreased. The protein concentration in liver and DL cells decreased mainly at 96 hr of treatment. It may be concluded that the natural product of D. pentagyna promises to be more active against Dalton's lymphoma than others and the decrease in glutathione level may be one of the important steps in resulting this antitumour effect.
Subject(s)
Ageratum , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Dilleniaceae , Glutathione/metabolism , India , Lymphoma/drug therapy , Mice , Phytotherapy , Plant Extracts/therapeutic use , Plants, Medicinal , Potentilla , TaxusABSTRACT
Changes in glutathione levels were determined in tissues of 11- to 12-week-old Swiss albino mice at different stages of Dalton's lymphoma tumor growth and following cisplatin (8 mg/kg body weight, ip) treatment for 24-96 h, keeping 4-5 animals in each experimental group. Glutathione levels increased in spleen of tumor-bearing compared to normal mice (9.95 ± 0.14 vs 7.86 ± 1.64 µmol/g wet weight, P0.05) but decreased in blood (0.64 ± 0.10 vs 0.85 ± 0.09 mg/ml) and testes (9.28 ± 0.15 vs 10.16 ± 0.28 µmol/g wet weight, P0.05). Dalton's lymphoma cells showed an increase in glutathione concentration (4.43 ± 0.26 µmol/g wet weight) as compared to splenocytes, their normal counterpart (3.62 ± 0.41 µmol/g wet weight). With the progression of tumor in mice, glutathione levels decreased significantly in testes (~10%) and bone marrow cells (~13%) while they increased in Dalton's lymphoma cells (28-46%) and spleen (15-27%). Glutathione levels in kidney, Dalton's lymphoma cells and bone marrow cells (8.50 ± 1.22, 4.43 ± 0.26 and 3.28 ± 0.17 µmol/g wet weight, respectively) decreased significantly (6.04 ± 0.42, 3.51 ± 0.32 and 2.17 ± 0.14 µmol/g wet weight, P0.05) after in vivo cisplatin treatment for 24 h. Along with a decrease in glutathione level, the glutathione-S-transferase (GST) activity also decreased by 60% in tumor cells after cisplatin treatment. The elevated drug uptake by the tumor cells under the conditions of reduced glutathione concentration and GST activity after treatment could be an important contributory factor to cisplatin's anticancer activity leading to tumor regression. Furthermore, lower doses of cisplatin in combination with buthionine sulfoximine (an inhibitor of glutathione synthesis) may be useful in cancer chemotherapy with decreased toxicity in the host
Subject(s)
Animals , Mice , Antineoplastic Agents , Cisplatin , Glutathione , Lymphoma , Antineoplastic Agents , Ascites , Cisplatin , Glutathione , Glutathione Transferase , Lymphoma , Spleen , Tumor Cells, CulturedABSTRACT
Sialic acid changes in Dalton's lymphoma cells and other tissues of 10-12-week-old Swiss albino mice were investigated in relation to tumour growth in vivo and following cyclophosphamide (ip, 200 mg/kg body weight) or cisplatin (ip, 8 mg/kg body weight) treatment. Three to four animals of both sexes were used in each experimental group. The sialic acid level of tumour cells (0.88 mmol/g) increased with tumour progression (1.44-1.59 mmol/g; P<=0.05) in mice. Sialic acid concentration in other tissues (liver, kidney, testes and brain) also increased (approximately 40, 10, 30 and 58 percent, respectively) in the tumour-bearing hosts as compared with that in the respective tissues of normal mice. In vivo cyclophosphamide or cisplatin treatment resulted in an overall decrease of sialic acid contents in the tissues. Cyclophosphamide was more efficient in lowering tissue sialic acid than cisplatin (P<=0.01, ANOVA). It is suggested that sialic acid residues could be an important factor contributing to the manifestation of malignant properties in cancer cells in general and Dalton's lymphoma cells in particular. A significant decrease in the sialic acid content of Dalton's lymphoma cells after cisplatin or cyclophosphamide treatment may bring about specific changes in tumour cells which could be associated with tumour regression
Subject(s)
Animals , Male , Female , Mice , Antineoplastic Agents , Ascites , Cisplatin , Cyclophosphamide , Lymphoma , N-Acetylneuraminic Acid , Antineoplastic Agents , Antineoplastic Agents, Alkylating , Biomarkers, Tumor , Brain , Cisplatin , Cyclophosphamide , Kidney , Liver , Lymphoma , Tumor Cells, CulturedABSTRACT
Cisplatin treatment brings about complete regression of ascites Dalton's lymphoma in mice. In the present study various steps involved during the tumor regression are examined using some biochemical and morphological parameters. During tumor regression, ascites fluid volume decreases sharply and there is an increase in carbohydrates and decrease in protein contents in the ascites supernatant after cisplatin treatment in vivo. Cisplatin treatment brings about definite changes in the arrangement/movement of surface membrane ruffles/blebs of tumor cells and causes infiltration of leukocytes (neutrophils, monocytes, lymphocytes) towards tumor cells. Membrane vesicles and vacuoles are also formed before the disintegration and lysis of tumor cells.