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.