Combination chemotherapy: synergistic inhibition of lymphoma L5178Y cells in culture and in vivo with 6-mercaptopurine and 6-(methylmercapto)purine ribonucleoside.

Paper

Combination chemotherapy: synergistic inhibition of lymphoma L5178Y cells in culture and in vivo with 6-mercaptopurine and 6-(methylmercapto)purine ribonucleoside.

Published Mar 1, 1969 · A. Paterson, A. Moriwaki

Cancer research

Q1 SJR score

26

Citations

1

Influential Citations

Semantic Scholar

Abstract

Summary The proliferation of cells of mouse lymphoma L5178Y, either in primary culture or in vivo , was inhibited much more effectively by combinations of 6-mercaptopurine and 6-(methylmercapto)purine ribonucleoside than would be expected from the separate effects of these agents. The existence of these synergistic inhibitory effects against the lymphoma cells in culture indicates that drug effects in the tumor cell, rather than effects at the host level, were responsible for the increase in survival time achieved by combining the drugs. In the most effective combinations of the drug pair, 6-mercaptopurine was in 5- to 10-fold molar excess, whether assayed in vivo or against cultured lymphoma cells. A likely biochemical mechanism for this synergism is discussed, based on the enhancement in 6-mercaptopurine anabolism caused by 6-(methylmercapto)purine ribonucleoside.

Study Snapshot

Combining 6-mercaptopurine and 6-(methylmercapto)purine ribonucleoside effectively inhibits mouse lymphoma L5178Y cell proliferation, potentially increasing survival time.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Combination chemotherapy: synergistic inhibition of lymphoma L5178Y cells in culture and in vivo with 6-mercaptopurine and 6-(methylmercapto)purine ribonucleoside.

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References

The enzymic formation of 6-(methylmercapto)purine ribonucleoside 5'-phosphate.

Me6MPR is efficiently phosphorylated in mouse tissues and Ehrlich ascites carcinoma cells, with no other major metabolites formed, suggesting its potential as a targeted therapy for cancer.

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This study presents a new method for screening antitumor compounds using in vitro-cultured Yoshida sarcoma cells, evaluating their antitumor effects by determining cytomorphological changes and inhibition of cell proliferation.

Citations

Sequence-, time- and dose-dependent synergism of methotrexate and 6-mercaptopurine in malignant human T-lymphoblasts.

Methotrexate and 6-mercaptopurine show synergistic action in malignant human T-lymphoblasts, depending on the concentration of MTX and the time and sequence of administration.

Synergistic interaction between acivicin (AT-125) and 6-thioguanine in the murine leukemia L1210. Biochemical and cytokinetic considerations.

Acivicinan pretreatment in murine leukemia L1210 cells potentiates the growth inhibitory effects of 6-thioguanine, potentially through biochemical and cytokinetic factors.

Effect of de novo purine synthesis inhibitors on 5-fluorouracil metabolism and cytotoxicity.

Inhibiting de novo purine synthesis, such as methotrexate, can enhance 5-fluorouracil accumulation and synergistic cytotoxicity in cancer cells.

Conversion of 6-thioguanine to the nucleoside level by purine nucleoside phosphorylase of sarcoma 180 and sarcoma 180/TG ascites cells.

Sarcoma 180 and Sarcoma 180/TG cells metabolize 6-thioguanine to 6-thioguanosine, which is crucial for cellular sensitivity to 6-thiopurines, and its efflux into the cellular environment may impact antineoplastic activity.

Effects of 6-thiopurines on the transforming activity of bacillus subtilis dexoyribonucleic acid.

6-mercaptopurine ( 6-MP) significantly decreases the transforming activity of Bacillus subtilis DNA, while 6-thioguanine ( 6-TG) and bromodeoxyuridine ( BUdR) show no effect, suggesting other mechanisms may be involved.

Multiple basis of combination chemotherapy

Combination chemotherapy benefits patients by increasing the effectiveness of active drugs, reducing toxicity, and selectively reversing toxicity.

THE STRUCTURE OF NUCLEOSIDES IN RELATION TO THEIR BIOLOGICAL AND BIOCHEMICAL ACTIVITY: A SUMMARY

Nucleoside analogs' diverse biological effects and biochemical targets make it difficult to predict their potential therapeutic value, despite their potential as useful therapeutic agents.

Biochemical mechanisms for the synergism between 6-thioguanine and 6-(methylmercapto)purine ribonucleoside in sarcoma 180 cells.

The synergism between 6-thioguanine and 6-(methylmercapto)purine ribonucleoside in Sarcoma 180 cells may involve effects on catabolism, synthesis of analog nucleotides, and sequential blockade of purine biosynthesis.

Synergistic effect of 6-mercaptopurine and 6-methylmercaptopurine ribonucleoside on the levels of adenine nucleotides of Sarcoma 180 cells.

The combination of 6-mercaptopurine and 6-methylmercaptopurine ribonucleoside effectively reduces adenine nucleotide levels in Sarcoma 180 cells, suggesting potential antitumor effects.