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Author Chu, Min ♦ Truumees, Imbi ♦ Rothofsky, Marnie L. ♦ Patel, Mahesh G. ♦ Gentile, Frank ♦ Das, Pradip R. ♦ Puar, Mohindar S. ♦ Lin, Stanley L.
Source J-STAGE
Content type Text
Publisher JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
Language English
Abstract Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene induction, have been isolated from the fermentation broth of the fungal culture (SCF-1168), Gliocladium sp. Along with compounds 1 and 2, a known compound verticillin A (3) was also obtained from the culture. Structure elucidation of 1 and 2, accomplished by analysis of spectral data in comparison with the data of 3, revealed both 1 and 2 were found to be closely related to the verticillin family of diketopiperazines. All three compounds prevented serum-stimulated transcription of the human c-fos promoter, using a fos/lac Z reporter gene assay, with $IC_{50}$ values of 1.5, 18 and 0.5μM for 1, 2 and 3, respectively. Northern analysis revealed that exposure of cells to compound 3 causes inhibition of both phorbol ester-induced c-fos induction and serum-induced JE induction in the absence of inhibiting RNA synthesis, as measured by $[^{3}H]uridine$ incorporation. These results suggest that this class of compounds exerts antitumor activity by blocking a signal transduction pathway that is common to and necessary for the induction of at least a subset of immediate early genes involved in cell proliferation.
ISSN 00218820
Learning Resource Type Article
Publisher Date 1995-12-25
e-ISSN 18811469
Journal The Journal of Antibiotics(antibiotics1968)
Volume Number 48
Issue Number 12
Page Count 6
Starting Page 1440
Ending Page 1445


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