In vitro modulation of human and murine melanoma growth by prostanoid analogues

Marvin D Bregman,Frank L Meyskens

doi:10.1016/0090-6980(83)90179-x

Abstract

The inhibitory effect of various prostaglandin analogues on the anchorage independent growth of murine and human melanoma cells was measured. PGA analogues (which were modified at C-16 and C-18) did not demonstrate any major improvement in activity over PGA alone. These included 16, 16-dimethyl PGA 1, 16,16-dimethyl-PGA 2, 16,16-dimethyl-18-oxa-PGA 2 and trans-δ-2-15-α acetoxy-16,16-dimethyl-18-oxa-11-deoxy-PGE 1-methylester. The thromboxane synthetase inhibitor, U51605, demonstrated weak anti-proliferative activity. PGD 2 (with a ketone at C-11 versus C-9 for PGA and PGE) was the most potent prostaglandin tested. Cells from melanoma lines displayed species differences in their sensitivities. PGA 1 and PGE 1 were the most potent inhibitors of the anchorage independent growth of murine melanoma cells. On human melanoma cells PGD 2 was the most active prostaglandin, 2–3 times more potent than PGA 1; PGE 1 was a very weak inhibitor.

Highlights

Prostaglandins, especially the A :?ries (l-3), are potent modulators of animal tumor cells, both in vitro (l-5) and in vivu [6,7,8,9,10]
We have recently reported on tE usrijf the bilayG s%?t agar assay to measure the effect of prostaglandins on anchorage-independent growth [4]
PGA2 had very little activity, which corresponded to its effect on human melanoma cells

Summary

Introduction

Prostaglandins, especially the A :?ries (l-3), are potent modulators of animal tumor cells, both in vitro (l-5) and in vivu [6,7,8,9,10]. The anchorage-independent growth of melanoma cells obtained directly from patients and human Imelanoma cell lines was arrested by PGAl [11]. The major problem in extending these observdtions to the clinic is that the concentrations and exposure times needed to produce irreversible inhibition of growth with these prostaglandins as single agent effrctors would be excessively toxic for patients [12]. With this in mind, structural analogues of PGAl were investigdted to determine their activity

Methods

Results

Conclusion