Prostaglandin Analogs as Inhibitors of Tumor Cell DNA Synthesis 1

Abstract

Abstract

Analogs of the A and E series prostaglandins were screened in vitro for their chemotherapeutic potential against Lewis lung carcinoma and B16 amelanotic melanoma cells, since in vivo studies had demonstrated that PGA₁ and an analog of PGE₂ inhibited tumor growth. DNA synthesis by collagenase-dispersed tumor cells was evaluated at timed intervals after exposure to the 16, 16-dimethyl analogs of PGA₁, PGA₂, PGE₁, and PGE₂. In general, the PGA derivatives were more potent than the PGE analogs. However, the maximum effect was achieved with combined PGA and PGE treatment. These findings demonstrate that A and E series prostaglandin analogs inhibit DNA synthesis in two unrelated tumor types and thus may be potent inhibitors of tumor growth. These effects were not due to tumor cell cytotoxicity. These results suggest that these compounds may prove useful as cancer chemotherapeutic agents.