The selective 5-lipoxygenase inhibitor A63162 reduces PC3 proliferation and initiates morphologic changes consistent...

We examined the effect of A63162 (Abbott), a selective inhibitor of 5-lipoxygenase on human prostate (PC3) cell proliferation. Within 5 min DNA synthesis was reversibly inhibited by 40 microM A63162, without altered cellular attachment or uptake of trypan blue. After 72 Hr, cells continued to be attached and exclude dye, were reduced in number and their histology was altered. Many treated cells were larger, more pleomorphic, with nuclear and cytoplasmic ultrastructural changes consistent with preparation for secretion. Some cells contained moderately swollen, distorted mitochondria. ETYA, a less selective inhibitor of 5-lipoxygenase that also inhibits cell replication, acutely reduced O2 uptake by 40%, but A63162 did not. The retention of the supravital mitochondrial dye, rhodamine 123 was increased by ETYA at 4 hr, but not after 24 hr; retention was not altered by A63162. Although the mechanism by which A63162 reversibly inhibits PC3 proliferation and initiates preparation for secretion is not identified, additional studies should further define its role in these events.