Abstract
Iejimalide B, a marine macrolide, causes growth inhibition in a variety of cancer cell lines at nanomolar concentrations. We have investigated the effects of Iejimalide B on cell cycle kinetics and apoptosis in the p53^+^/AR^+^ LNCaP and p53^β^/AR^β^ PCβ3 prostate cancer cell lines. Iejimalide B, has a dose and time dependent effect on cell number (as measured by crystal violet assay) in both cell lines. In LNCaP cells Iejimalide B induces a dose dependent G~0~/G~1~ arrest and apoptosis at 48 h (as measured by ApoβBrdU staining). In contrast, Iejimalide B initially induces G~0~/G~1~ arrest followed by S phase arrest but does not induce apoptosis in PCβ3 cells. qPCR and Western analysis suggests that Iejimalide B modulates the steady state level of many gene products associated with cell cycle (including cyclins D, E, and B and p21^waf1/cip1^) and cell death (including survivin, p21B and BNIP3L) in LNCaP cells. In PCβ3 cells Iejimalide B induces the expression of p21^waf1/cip1^, down regulates the expression of cyclin A, and does not modulate the expression of the genes associated with cell death. Comparison of the effects of Iejimalide B on the two cell lines suggests that Iejimalide B induces cell cycle arrest by two different mechanisms and that the induction of apoptosis in LNCaP cells is p53βdependent. J. Cell. Biochem. 105: 998β1007, 2008. Β© 2008 WileyβLiss, Inc.