A common feature of both apoptosis and inflammation is the activation of caspases. Caspases are aspartate-directed cysteine proteases that have numerous cellular targets. It has been discovered that several flavonoids are inhibitors of caspases. Flavonoids are members of a family of polyphenolic compounds from plants that have many biological properties, one of which is the ability to induce cell death. Some flavonoids are selective inhibitors of particular caspases. Since some of the inhibitory flavonoids are nevertheless cytotoxic, these results suggest that flavonoid-induced cell death may be occurring through a non-classical apoptosis pathway that is not dependent on caspase activity.

Flavonoids are polyphenolic plant natural products found extensively in the human diet. This class of compounds has been of considerable medicinal interest because of numerous reports of anti‐inflammatory and anti‐cancer activities. However, a detailed understanding of the biochemical mechanism of these activities is lacking because the compounds have been reported to be antioxidants and also affect multiple cell signaling pathways, including those mediated by protein kinase C, phosphoinositide 3‐kinase, Akt/protein kinase B, tyrosine kinases, and mitogen activated protein kinase.We have undertaken a study to determine which of the various cellular activities are necessary and sufficient to induce cell death in a variety of breast cancer cell lines. As part of this study, we have evaluated the ability of various flavonoids to induce apoptosis by evaluating their effect on various markers, including caspase 3/7 activation, and cytochrome C release from the mitochondria. We have found that several flavonoids, in addition to inducing cell death are inhibitors of caspase 3. This poster will report the details of our studies on the inhibition of caspases by flavonoids.Support of research was through the National Institutes of Health RISE Program at San Jose State University to JB.