Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gambogic acid (GA), a natural xanthone, has a wide spectrum of pharmacological activities, including repression of telomerase expression and induction of apoptosis of cancer cells. GA has also been reported to reduce the steady-state level of thymidylate synthetase mRNA in a gastric carcinoma cell line. Therefore, it has recently emerged as a candidate for use in cancer treatment. Using hepatoma cells with a dihydrofolate reductase (DHFR) gene amplification and cells transfected with an inducible DHFR transgene, we observed a negative relationship between DHFR expression and resistance to GA. Furthermore, DHFR assays in vitro indicated that in the presence of GA, DHFR activity was slightly inhibited and the affinity of the enzyme for dihydrofolate was markedly decreased. Treatment of rat hepatoma and other human and murine cancer cell lines with methotrexate and GA revealed that the two drugs displayed a marked synergistic lethal effect.
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PMID:Interaction between Gambogic acid and dihydrofolate reductase and synergistic lethal effects with methotrexate on hepatoma cells. 2326 38