Genistein inhibited proliferation and induced apoptosis in acute lymphoblastic leukemia, lymphoma and multiple myeloma cells<i>in vitro</i>

Abstract

Genistein is one of the major isoflavones in soy products. It has been reported that genistein has apoptotic effects on certain hematological malignancies. However, so far there have been no completely comparative studies of the effect of genistein on malignant hematological diseases, especially multiple myeloma. We investigated genistein's inhibitory effect on the growth of acute lymphoblastic leukemia (RS4;11 and CEM), lymphoma (Toledo and GA10) and multiple myeloma (OPM-2 and U266) cell lines in vitro. We observed that genistein dose- and time-dependently inhibited proliferation of these cells. The cell line sensitivity to genistein treatment based on the 50% inhibitory concentration (IC(50)) values in decreasing order of toxicity was found to be as follows: RS4;11 (4.89 ± 4.28 μM) > GA10 (13.08 ± 3.49 μM) > Toledo (16.94 ± 3.89 μM) > CEM (17.31 ± 0.72 μM) > OPM-2 (46.76 ± 2.26 μM) > U266 (128.82 ± 1.90 μM). The mechanism of growth inhibition was through induction of apoptosis and cell cycle arrest. The concomitant altered expression of apoptosis pathway proteins and cell cycle modulators (caspases 9, 3, 7, PARP [poly(ADP-ribose) polymerase], cIAP1 [inhibitor of apoptosis protein 1], Bcl-2 and cyclin B1) were observed by Western blot and real-time polymerase chain reaction (PCR) analyses. In addition, some malignancy-related embryologic pathway proteins, e.g. Notch1 and Gli1, were modulated by genistein treatment in sensitive cell lines.