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Cytotoxicity of Aliphatic Acetogenin Analogs against two of the most Aggressive Solid Tumors
Author(s) -
Leon Leticia G,
Giovannetti Elisa,
Alecci Claudia,
Giancola Fiorella,
Funel Niccola,
Zucali Paolo,
Peters Godefridus J,
Padrón José Manuel
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.763.4
Previous research demonstrated health benefits of avocados, and recent studies showed that Avocados have a high content of phytochemicals with potential chemopreventive activity. Avocado extracts can also inhibit the growth of different tumor cells and the β′‐acetoxy‐α,β‐unsaturated ketones derivates from avocado could be promising pharmacophores for the design of new anticancer drugs. Thus, the aim of this study was to evaluate the cytotoxic activity of three active β′‐acetoxy‐α,β‐unsaturated ketones (1, 2, 3) against several cell lines derived from two chemoresistant tumor types, mesothelioma and pancreatic ductal cancer. These compounds displayed GI50 values in the range of 1.7–28.8 μM against a panel of three MPM and four pancreatic tumor cell lines. Furthermore, they caused a clear dose‐dependent cell cycle arrest in the S and G2/M phases after 24h exposure, while more to 30% of the cell accumulated in the subG1 phase indicative for apoptotic cell death. These results indicate that linear β′‐acetoxy‐α,β‐unsaturated ketones are promising pharmacophores for the design of new anticancer drugs. Research supported by MICIIN (CTQ2008‐06806‐C02‐01/BQU), MSC(RTICC RD06/0020/1046), ACIISI (PI 2007/021), FUNCIS(PI 01/06, 35/06, 43/09). L.G.L.:MSC‐FIS contract. J.M.P.:MEC‐FSE RyC contract.