Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines.

Six flavonoids [xanthohumol (XN), 2',4',6',4-tetrahydroxy-3'-prenylchalcone (TP); 2',4',6',4-tetrahydroxy-3'-geranylchalcone (TG); dehydrocycloxanthohumol (DX); dehydrocycloxanthohumol hydrate (DH); and isoxanthohumol (IX)] from hops (Humulus lupulus) were tested for their antiproliferative activity in human breast cancer (MCF-7), colon cancer (HT-29) and ovarian cancer (A-2780) cells in vitro. XN, DX and IX caused a dose-dependent (0.1 to 100 microM) decrease in growth of all cancer cells. After a 2-day treatment, the concentrations at which the growth of MCF-7 cells was inhibited by 50% (IC50) were 13.3, 15.7 and 15.3 microM for XN, DX and IX, respectively. After a 4-day treatment, the IC50 for XN, DX and IX were 3.47, 6.87 and 4.69 microM, respectively. HT-29 cells were more resistant than MCF-7 cells to these flavonoids. In A-2780 cells, XN was highly antiproliferative with IC50 values of 0.52 and 5.2 microM after 2 and 4 days of exposure, respectively. At 100 microM, all the hop flavonoids were cytotoxic in the three cell lines. Growth inhibition of XN- and IX-treated MCF-7 cells was confirmed by cell counting. XN and IX inhibited DNA synthesis in MCF-7 cells. As antiproliferative agents, XN (chalcone) and IX (flavanone isomer of XN) may have potential chemopreventive activity against breast and ovarian cancer in humans.