Lignans and flavonoids as apoptosis inducers

Apoptosis is an important mode of „programmed“ cell death, which involves the genetically determined elimination of cells. As a vital component of normal cell turnover, inappropriate apoptosis is a factor in many human diseases including cancer, where unwanted cells are unable to be eliminated by the body. Many anticancer drugs today act by way of apoptosis induction [1]. In our ongoing search for bioactive molecules from medicinal plants [2], fifteen phenolic compounds, including lignans and flavonoids were assayed for their apoptosis induction activity on (HuH-7) human liver cancer cells. The lignans, including six dibenzylbutanes and one butirolactone were isolated previously from the dichloromethane extract of Pycnanthus angolensis or obtained by derivatization [3,4]. Further studies on the ethyl acetate extract of this species have led to the isolation of seven isoflavones and one flavanone. Their structures were identified based on spectroscopic methods including 2D NMR experiments. Methodology for apoptosis detection included cell viability assays, nuclear morphology evaluation, and general caspase-3-like activity assessments. The compounds tested at a concentration of 20µM showed varying degrees of apoptosis induction activity after 24h exposure. Caspase activity assays confirmed these results.

Acknowledgements: This study was supported by a fellowship from FCT, Portugal (reference number SFRH/BPD/30492/2006).

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3. Abrantes M. et al. (2008) Planta Med. 74: 1408–1412.

4. Duarte N. Et al. (2010) Planta Med. DOI: 10.1055/s-0029–1240892.