Prostaglandin Analogs as Inhibitors of Tumor Cell DNA Synthesis

Abstract

Analogs of the A and E series prostaglandins [PG] [16,16-dimethyl-PGA1, PGA2, PGE, and PGE2] were screened in vitro for their chemotherapeutic potential against mouse 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. A and E series PG analogs inhibit DNA synthesis in 2 unrelated tumor types and thus may be potent inhibitors of tumor growth. These effects were not due to tumor cell cytotoxicity. These compounds may prove useful as cancer chemotherapeutic agents.