MEN15658: a new promising anti-tumoral drug active on resistant tumor cells.
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.
Salvatore
Carmela
C
Department of Pharmacology, Menarini Ricerche SpA, V. Tito Speri 10, 00040 Pomezia, Rome, Italy.
Binaschi
Monica
M
Bigioni
Mario
M
Camarda
Grazia
G
Maggi
Carlo Alberto
CA
Goso
Cristina
C
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005544:Forecasting; D020869:Gene Expression Profiling / Q000379:methods; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000473:pathology; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006835:Hydrazones; D047908:Intracellular Signaling Peptides and Proteins; D010618:Phenanthrolines; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D000097642:GADD45 Proteins; C493510:2-((1,10)phenanthrolin-2-ylhydrazono)-3,4-dihydro-2H-naphthalen-1-one; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse