Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:38966-21-1 (Aphidicolin)
 236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aphidicolin (AP) or hydroxyurea (HU) inhibited DNA repair and enhanced cytotoxicity in human ovarian carcinoma cells A2780 treated with L-phenylalanine mustard (L-PAM) combined with cisplatin or thioTEPA, and in the cells treated with cisplatin combined with thioTEPA. In cultures treated with L-PAM or cisplatin alone post-treatment with AP or HU had no effect on DNA repair and produced only additive cytotoxicity. Post-treatment with AP + HU inhibited DNA repair and enhanced cell killing in cultures treated with L-PAM alone. The inhibitor of protein synthesis cycloheximide protected cells from the cytotoxicity of AP + HU but had no effect on synergistic cell killing produced by DNA repair inhibition. In cisplatin-resistant cells A2780/CP post-treatment with AP + HU enhanced the cytotoxicity of L-PAM, but not of cisplatin. However, in resistant cells treated with cisplatin combined with L-PAM or thioTEPA DNA repair inhibitors decreased IC90 of cisplatin. Treatment of cells with two alkylating agents enhanced the sensitivity to DNA repair inhibitors and eliminated low sensitivity to inhibitors of repair associated with drug resistance.
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PMID:Inhibition of DNA repair in cells treated with a combination of alkylating agents. 835 64

Murine fibrosarcoma L929 cells were transfected with human Fas cDNA. The mode of cell death was analysed following treatment either with tumour necrosis factor (TNF) or with agonistic antibodies to Fas. While triggering of the TNF receptors led to necrosis, clustering of the Fas antigen resulted in apoptotic cell death. N-tosyl-l-phenylalanine chloromethyl ketone and Nalpha-p-tosyl-l-lysine chloromethyl ketone, two serine protease inhibitors, has a protective effect on TNF-induced killing, while Fas-mediated cell death was rather enhanced. Lithium chloride, which had a synergistic effect on TNF cytotoxicity, did not affect Fas-mediated death, whereas staurosporine had an enhancing effect on both types of cell death. Aphidicolin and hydroxyurea, inhibitors of DNA synthesis, were able to sensitize cells to Fas-induced killing, but had no effect on TNF cytotoxicity. Finally, we demonstrate that the effect of increasing concentrations of actinomycin D or cycloheximide is very different for the two types of cell killing. We conclude that either necrosis or apoptosis can occur in the same cell type, depending on the trigger, and that, although both pathways perhaps may share some cellular components, signal transduction is different for the two types of cell death.
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PMID:Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells. 936 40