Anti‐proliferate Effects of a Marine Macrolide on Cell Cycle Kinetics, Apoptosis, and Gene Expression in LNCaP and PC‐3 Cells

TL;DRAbstract

Iejimalide B (IejB) is a marine macrolide produced by Eudistoma cf. rigida, a sea slug living in the waters near the Japanese island, Ie Jima. We are investigating the effects of IejB on cell cycle kinetics and apoptosis, as well as its effect on gene expression in the prostate cancer cell lines, LNCaP and PC‐3 cells. IejB has a dose and time dependent effect on cell number in both PC‐3 and LNCaP cells. In p53‐/AR‐ PC‐3 cells, IejB induces a G1/S phase arrest at 24 h and causes a transition to S phase arrest at later time points. In comparison, IejB induces G0/G1 phase arrest and apoptosis (Apo‐BrdU staining) in the p53+/AR+ LNCaP cells. These data suggest that IejB exerts its effects by initially inhibiting the cell cycle in G0/G1 and subsequently induces S phase arrest by inhibiting DNA synthesis. Since the induction of apoptosis in LNCaP cells occurs without entry into S phase, IejB appears to have two targets within the cell: one at the bifurcation of the cell cycle and apoptotic p

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