MEN15658: a new promising anti-tumoral drug active on resistant tumor cells.

Abstract

We describe the identification of MEN15658, a molecule characterized by a promising cytotoxic effect against human tumor cell lines, including platinum- and anthracycline-resistant ovarian carcinoma. MEN15658 induces p53 accumulation, and activation of gadd-45, p21, c-fos and bcl-2 family genes in human ovarian carcinoma A2780 cell line. The compound causes a block in S phase of the cell cycle, inducing apoptotic cell death, thus suggesting an involvement of DNA damage in the MEN15658 effect on tumor cells. The anti-tumoral activity observed against the human ovarian carcinoma A2780 cell line xenotransplanted in nude mice makes this compound a new promising anti-tumoral drug.

• Authors: Carmela Salvatore, Monica Binaschi, Mario Bigioni, Grazia Camarda, Carlo Alberto Maggi, Cristina Goso
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 15 Issue 2 Pg. 151-6 (Feb 2004) ISSN: 0959-4973 [Print] England
• PMID: 15075671 (Publication Type: Journal Article)

Chemical References

• 2-((1,10)phenanthrolin-2-ylhydrazono)-3,4-dihydro-2H-naphthalen-1-one
• Antineoplastic Agents
• CDKN1A protein, human
• Cdkn1a protein, mouse
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• GADD45 protein
• Hydrazones
• Intracellular Signaling Peptides and Proteins
• Phenanthrolines
• Proteins
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-fos

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Cell Survival (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (drug effects, genetics, metabolism)
• Drug Resistance, Neoplasm (drug effects, genetics, physiology)
• Drug Screening Assays, Antitumor (methods)
• Female
• Forecasting
• Gene Expression Profiling (methods)
• Genes, p53 (drug effects, genetics, physiology)
• Humans
• Hydrazones (chemistry, pharmacology, therapeutic use)
• Intracellular Signaling Peptides and Proteins
• Lung Neoplasms (pathology)
• Mice
• Mice, Nude
• Ovarian Neoplasms (pathology)
• Phenanthrolines (chemistry, pharmacology, therapeutic use)
• Proteins (drug effects, genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (drug effects, genetics, metabolism)
• Proto-Oncogene Proteins c-fos (drug effects, genetics, metabolism)
• S Phase (drug effects)
• Time Factors
• Transplantation, Heterologous (methods)
• Tumor Cells, Cultured