Effects of Iejimalide B, a marine macrolide, on growth and apoptosis in prostate cancer cell lines.
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-/AR- PC-3 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 G0/G1 arrest and apoptosis at 48 h (as measured by Apo-BrdU staining). In contrast, Iejimalide B initially induces G0/G1 arrest followed by S phase arrest but does not induce apoptosis in PC-3 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 PC-3 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 p53-dependent.
Wang
Wei-Lin Winnie
WL
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA.
McHenry
Peter
P
Jeffrey
Randy
R
Schweitzer
Dirk
D
Helquist
Paul
P
Tenniswood
Martin
M
D017209:Apoptosis / Q000187:drug effects*; D002219:Carbamates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007399:Interphase; D007700:Kinetics; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D016159:Tumor Suppressor Protein p53
D002219:Carbamates; D018797:Cell Cycle Proteins; D018942:Macrolides; D016159:Tumor Suppressor Protein p53; C520301:iejimalide B