In-vitro effects of antineoplastic prostaglandins on human leukemic cell growth and normal myelopoiesis

Abstract

The effects of prostaglandin (PG)E 1, PGD 2 and 9-deoxy-Δ 9-PGD 2 (PGJ 2) on the clonogenic growth of six kinds of human leukemic cell lines (K562, KG1, HL60, U937, THP1 and Molt4) and normal human myeloid progenitor cells (CFU-GM) were studied using semisolid agar cultures. While the degree of suppression of leukemic growth by PGE 1 varied from cell line to cell line, PGD 2 and PGJ 2 equally suppressed the growth of all leukemic cell lines. The potency of growth inhibition was as follows: PGJ 2 > PGD 2 > PGE 1. The increase of cellular cAMP level induced by prostaglandin treatment did not parallel their cytotoxic potency. Normal myeloid colony formation was also suppressed by PGE 1, PGD 2 or PGJ 2. In contrast to the preferential inhibition of macrophage colony formation by PGE 1 such lineage-selective suppression was not observed for PGD 2 or PGJ 2. These findings suggest that PGD 2 and PGJ 2 potently inhibit the leukemic growth by a different mechanism from that of PGE 1 and by a cAMP-independent mechanism. These prostaglandins seem to be promising chemotherapeutic agents for acute leukemia.