Requirement of a reactive α,β-unsaturated carbonyl for inhibition of tumor growth and induction of differentiation by “A” series prostaglandins

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Abstract

Prostaglandins of the A series have been reported to inhibit tumor cell growth and induce tumor cell differentiation by a yet unknown mechanism. We propose that these effects are due to the presence of a reactive α,β-unsaturated carbonyl group (Δ10,11) in the cyclopentane ring of the PGA molecule. PGA was effective whereas PGB (sterically hindered α,β-unsaturated carbonyl at Δ8,12) and PGA conjugated to glutathione were ineffective. 15-Epi-PGA2 was as effective as PGA2 suggesting that the S absolute configuration of the 15-hydroxyl group is not essential. There was no correlation between generation of cAMP and inhibition of cell proliferation or induction of differentiation by various prostaglandins. The data suggest that PGA's and PGA-like compounds inhibit tumor cell growth and induce differentation because of the chemical reactivity of the α,β-unsaturated carbonyl rather than hormonal activity of the prostanoid nucleus.

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