Effect of endogenous and exogenous prostaglandin E on Friend erythroleukaemia cell growth and differentiation

Abstract

Summary.-The effect of exogenous and endogenous prostaglandins on the patterns of growth and differentiation of Friend erythroleukaemia cells (FLC) were studied. During the differentiation process, DMSO stimulated PGE synthesis by an average of 95o%. The addition of a long-acting synthetic analogue of PGE2, 16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) to the culture medium only slightly and temporarily slowed cell growth, with no appreciable induction of differentiation. However, in the presence of DMSO, the same concentration of di-M-PGE2 produced 73 0 inhibition of cell growth and accelerated and potently stimulated haemoglobin production. The action of both di-M-PGE2 and DMSO on cell proliferation was dependent upon the state of cell growth at the time of the administration of these compounds. FLC cultures treated with DMSO+di-M-PGE2 produced considerable amounts of haemoglobin before even one duplication cycle was completed. Both DMSO and di-M-PGE2 stimulated endogenous PGE biosynthesis, and the biosynthetic effect of these compounds was synergistic.Inhibition of endogenous prostaglandin synthesis by indomethacin completely abolished the effects produced by DMSO+di-M-PGE2 on the growth, and substantially reduced the stimulated differentiation of FLC. These data suggest that an endogenously synthesized prostaglandin plays a significant role in both the inhibition of replication and in the stimulation of differentiation induced by DMSO and di-M-PGE2 in Friend erythroleukaemia cells.

Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones

“…Some PGs enhance the differentiation of human myeloid leukemia cells, although their differentiation-inducing activities are not so prominent. [6][7][8] However, it is still possible that some PG analogs and their related compounds may potently induce the differentiation of leukemia cells. A recent report indicated that methyl jasmonate (MJ) inhibits the growth of some lymphoid malignant cells in vitro and in vivo.…”

Inhibition of Friend erythroleukaemia-cell tumours in vivo by a synthetic analogue of prostaglandin E2

“…Inoculation of mice with FLC pretreated in vitro with DMSO for at least 72 h produces smaller tumours and permits longer survival than untreatedcell inocula (Friend et al, 1971;Preisler et al, 1976). In a recent study we demonstrated that endogenously synthesized PGE was involved in the regulation of the proliferation and differentiation of FLC in vitro (Santoro et al, 1979). Moreover, the addition of the long-acting analogue di-M-PGE2 to the culture medium pro-fouiidly inhibited the growth and stimulated the differentiation (measured as haemoglobin production) of DMSO-treated cells.…”

“…Since thiu effect was not seen in mice inoculated with undifferentiated cells, the data suggesi that di-M-PGE2 acts directly on the replication of tumour cells, rather than on factors related to host response. It is interesting that the in vitro studies (Santoro et al, 1979) also demonstrated thai DMSO-treated FLC are much more sensitive to di-M-PGE2 than undifferentiated cells. In fact, the latter were not affected by di-M-PGE2, even at higher concentrations (50 jg/ml).…”

Cyclooxygenase 2 and prostaglandin E2 regulate the attachment of calcium oxalate crystals to renal epithelial cells

“…11,12 However, in these experiments, PGE2 was exogenously added to the cells, and the effect of exogenous PGE2 might be different from that of endogenously produced PGE2. 13 Furthermore, in this type of study, PGE2 requires a solvent and must be replenished each time the medium is changed.…”