ABSTRACT
Combination chemotherapy studies were carried out in vivo against sarcoma 180 (ascites)(S180) and Ehrlich (ascites) carcinoma (EAC) tumours using cytotoxic drugs and methoxyphenyl maleamic acid (MPMA), an intermediate in the synthesis of pyrrolidine-nitrogen-mustards. Preliminary data have suggested that the combination of 5-fluorouracil (5-FU) and methoxyphenyl maleamic acid (MPMA) was more active than 5-FU used singly against EAC tumour. The possible therapeutic potential of this combination was further investigated in EAC tumour.
Subject(s)
Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ehrlich Tumor/drug therapy , Drug Therapy, Combination , Female , Fluorouracil/administration & dosage , Male , Maleates/administration & dosage , Mice , Random Allocation , Sarcoma 180/drug therapyABSTRACT
The anti-tumour effects of methoxyphenyl maleamic acid (MPMA) and cytotoxic drugs, in combination were investigated on P388 leukaemia and S180 (ascites) tumours. Simultaneous administration of MPMA with CTX or HN2 resulted in enhancement of anti-tumour activity. The increased activity was observed against P388 leukaemia, whereas S180 (ascites) tumour was not responsive to the combined treatment. The possible mechanism (s) of action, responsible for the modulation of activity of CTX and HN2 against P388 tumour have been postulated.
Subject(s)
Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ascites/drug therapy , Cyclophosphamide/administration & dosage , Drug Synergism , Leukemia P388/drug therapy , Maleates/pharmacology , Mechlorethamine/administration & dosage , MiceABSTRACT
The cytotoxic effects of acetylated oil of Semecarpus anacardium nuts on the cells of P388 lymphocytic leukemia were tested in vitro. The product was tested at the concentrations ranging from 15-75 micrograms/ml. The cell kill was observed as early as three hr after the treatment. The effects of acetylated oil on the biosynthesis of DNA, RNA and protein using labelled thymidine, uridine and leucine respectively showed that the product inhibited the biosynthesis of all the three. This was indicated by the inhibition of the incorporation of their precursors. The uptake of 3H-thymidine was inhibited 15 min after treatment; while that of 3H-uridine and 14C-leucine took 30 and 45 min respectively. Since the S. anacardium oil was unstable due to air-oxidation, the studies were confined to its acetylated product.
Subject(s)
Acetylation , Animals , Antineoplastic Agents, Phytogenic , DNA, Neoplasm/metabolism , Female , India , Leukemia P388/drug therapy , Male , Mice , Mice, Inbred DBA , Neoplasm Proteins/metabolism , Oils/pharmacology , RNA, Neoplasm/metabolism , Time FactorsABSTRACT
Semecarpus anacardium Linn.f. nuts were extracted by using non-polar and polar organic solvents. Hot methanol extract and a resinous fraction, isolated from it, showed antitumour activity against P388 lymphocytic leukaemia in BDF1 mice as judged by their median survival time. Petroleum ether extract and its chromatographically isolated fraction were obtained. The latter fraction was distilled under reduced pressure to get an orange-coloured oil, (b.p. 200-20 degrees/2-3 mm). Both had antitumour activity. The orange-coloured oil, on further distillation under reduced pressure, yielded Bhilawanol. An acetyl derivative of the oil was also obtained. The latter two also had antitumour activity.