Effect of E-2-(4'-methoxybenzylidene)-1-benzosuberone on the 7,12-dimethylbenz[alpha]anthracene-induced onco/suppressor gene action in vivo II: A 48-hour experiment.
The cyclic chalcone analogue, E-2-(4'-methoxybenzylidene)-1-benzosuberone (MBB), has been found to show outstanding in vitro cytotoxic activity against P388, L1210, Molt 4/C8 and CEM cells, as well as against a panel of human cell lines. In order to determine whether this promising antineoplastic activity would extend to anticarcinogenic properties, the effect of MBB on the 7,12-dimethylbenz [alpha]anthracene (DMBA)-induced expression of the c-myc, Ha-ras and p53 genes in isolated RNA from the liver, lung, kidney, spleen, thymus, lymph nodes and bone marrow of CBA/Ca inbred mice was investigated. Earlier we had found that administration of MBB can reduce the DMBA-induced 24-hour gene expressions most effectively when it is administered prior to, or simultaneously with, the DMBA-treatment to female CBA/Ca inbred mice. As a continuation of this study, we investigated the effect of MBB on the DMBA-induced gene expressions according to the two protocols in a 48-hour experiment. The 48-hour experiment with female and male CBA/Ca inbred mice also determined the compound which effectively reduced the DMBA-induced c-myc and Ha-ras overexpressions in almost all tissues. While the DMBA-induced gene expressions showed very different patterns, the effectiveness of the two different administrations of MBB was found to be very similar in the two sex groups. At the same time, contrary to the 24-hour experiment, increased p53 gene expression levels could be seen in several tissues in both sex groups. In order to get a better understanding of the effects of MBB on the DMBA-induced gene expressions "long-term" and "follow-up" studies should be performed.
Perjési
P
P
Department of Medical Chemistry, University Medical School of Pécs, Hungary.
Gyöngyi
Z
Z
Bayer
Z
Z
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D003508:Cycloheptanes / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009857:Oncogenes / Q000187:drug effects* / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism*
C407507:2-(4'-methoxybenzylidene)-1-benzosuberone; D000840:Anisoles; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D003508:Cycloheptanes; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene