An investigation into the anticancer effects and mechanism of action of hop ß-acid lupulone and its natural and synthetic derivatives in prostate cancer cells.

Lupulone, a ß-acid derived from hop extracts has been shown to exhibit antibacterial and anticancer activity. In this study we investigated the anticancer potency of lupulone and its novel derivatives and their mechanism of action on prostate cancer cells. Cell viability was determined using the MTT assay, and the ELISA approach was used to investigate induction of apoptosis. Immunoblot analysis was carried out to determine activation and regulation of proteins associated with cell death. Screening of natural and new lupulone derivatives for their anticancer activity demonstrated that one (lupulone derivative 1h) displayed stronger anticancer activity than lupulone itself on PC3 and DU145 prostate cancer cells. We further found that lupulone derivatives induced caspase-dependent apoptosis that is associated with activation of caspases 8, 9, and 3. Furthermore, caspase 8 inhibitor Z-IETD-fmk reduced cell death induced by lupulone derivatives, suggesting that apoptosis is mediated by caspase 8. Finally, we found that lupulone and its synthetic derivatives also increased formation of LC3II suggesting that autophagy is also implicated in prostate cancer cell death. The new lupulone derivatives induce caspase-dependent apoptosis and autophagy in prostate cancer cells and appear to be good candidates for further preclinical studies of prostate cancer treatment.

An efficient asymmetric synthesis of the potent beta-blocker ICI-118,551 allows the determination of enantiomer dependency on biological activity.

A highly efficient, practical and flexible two-step asymmetric synthesis of the beta(2)-selective beta-blocker ICI 118,551 is reported, allowing an unambiguous determination of the dependency of biological activity with optical activity, revealing the S,S-enantiomer to be the most potent.