Effect of E-2-(4'-methoxybenzylidene)-1-benzosuberone on the 7,12-dimethylbenz[alpha]anthracene-induced onco/suppressor gene action in vivo. I: A 24-hour experiment

Anticancer Res. 2000 Jan-Feb;20(1A):475-81.

Abstract

The cyclic chalcone analogue, E-2-(4'-methoxybenzylidene)-1-benzosuberone (MBB), was found to show outstanding in vitro antineoplastic activity against P388, L1210, Molt 4/C8 and CEM cells as well as against a panel of human tumor cell lines. In order to determine whether this promising antineoplastic activity would extend to anticarcinogenic properties, the effects of MBB on the 7,12-dimethylbenz[alpha] anthracene (DMBA)-induced expression of c-myc, Ha-ras and p53 genes in isolated RNA from liver, lung, kidney, spleen, thymus, lymph nodes and bone marrow of CBA/Ca inbred mice was investigated. DMBA is a well-known chemical carcinogen, which can act as an initiator by causing point mutations in certain oncogenes and tumor suppressor genes. Elevated expression of oncogenes after treatment with DMBA and other carcinogenic chemicals has been noted previously. Administration of MBB simultaneously with DMBA, 24 hours prior to or 24 hours after the DMBA treatment characteristically modified the DMBA-induced expression of the three genes in the 24-hour experiments. The most pronounced suppression effect of MBB could be observed in almost all the investigated tissues when it was administered simultaneously with DMBA. These "short-term" in vivo results support our previous conclusion that MBB can serve as a model molecule for subsequent structural modifications in searching for new effective anticarcinogenic agents.

Publication types

  • Comparative Study

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / antagonists & inhibitors
  • 9,10-Dimethyl-1,2-benzanthracene / pharmacology*
  • Animals
  • Anisoles / chemical synthesis
  • Anisoles / pharmacology*
  • Anticarcinogenic Agents / chemical synthesis
  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Carcinogens / pharmacology*
  • Cycloheptanes / chemical synthesis
  • Cycloheptanes / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects*
  • Genes, myc / drug effects*
  • Genes, p53 / drug effects*
  • Genes, ras / drug effects*
  • Kidney / drug effects
  • Kidney / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred CBA
  • Molecular Structure
  • Organ Specificity
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins p21(ras) / biosynthesis
  • RNA, Messenger / biosynthesis
  • Spleen / drug effects
  • Spleen / metabolism
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Tumor Suppressor Protein p53 / biosynthesis

Substances

  • 2-(4'-methoxybenzylidene)-1-benzosuberone
  • Anisoles
  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Carcinogens
  • Cycloheptanes
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • 9,10-Dimethyl-1,2-benzanthracene
  • Proto-Oncogene Proteins p21(ras)