Ingenol derivatives inhibit proliferation and induce apoptosis in breast cancer cell lines.
We present an analysis of the antitumour effects of a library of ingenol derivatives synthesized in our laboratory and published elsewhere. Fluoro-ingenol (1), ingenol-20-deoxy-20-phtalimido (2), ingenol-3-benzoate-20-deoxy-20-benzamide (3), ingenol-3-benzoate (4), ingenol-3,5-dibenzoate (5), ingenol-3,20-dibenzoate (6), 20-deoxy-20-benylureidoingenol-3-benzoate (7), ingenol-20-deoxy-20-fluoro-3-benzoate (8), ingenol-20-deoxy-20-fluoro-3,5-dibenzoate (9), ingenol-20-phenylcarbamate (10), ingenol-20-benzoate (11), ingenol-3-benzoate-20-phenylcarbamate (12) were tested in vitro on two well characterized breast cancer cell (BCC) lines, namely T47D and MDA-MB-231, as representative of two opposite types of hormone-sensitiveness and differentiation stage. These experiments led us to identify ingenol-20-benzoate (11) as a promising antitumour compound characterized by a relevant inhibition of cell growth and apoptotic cell death involving a p53-mediated pathway.
Vigone
A
A
Department of Obstetrics and Gynecology, Maggiore della Carità Hospital, Novara, Italy.
Tron
G C
GC
Surico
D
D
Baj
G
G
Appendino
G
G
Surico
N
N
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects
D000970:Antineoplastic Agents; D004224:Diterpenes; D016159:Tumor Suppressor Protein p53; C008125:ingenol