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Cell Cycle Effects of Prostaglandins A₁, A₂, and D₂ in Human and Murine Melanoma Cells in Culture

Cancer Research, The Upjohn Company, Kalamazoo, Michigan 49001

Our interest in prostaglandins (PGs) as antitumor agents stemmed from the report of Bregman and Meyskens (Cancer Res., 43: 1642–1645, 1983) that PGA₁, PGA₂, and PGD₂ inhibited colony formation by human melanoma cells obtained from fresh biopsies of melanoma patients. We tested several PGs and found that PGA₁, PGA₂, and PGD₂ were the most cytotoxic to L1210 cells in culture. Therefore, we studied these PGs for their effects on growth, cell survival, and cell progression of murine (B16) and human (RPMI 7932, SK Mel 28) melanoma cells in culture. Although the three PGs equally inhibited the growth of B16 cells, PGD₂ was more inhibitory to RPMI 7932 or SK Mel 28 than PGA₁ or PGA₂. Similarly the three PGs were almost equally active in inhibiting colony formation by B16 cells. However, against human melanoma cells, PGD₂ was much more active than PGA₁, whereas PGA₂ was inactive. Towards the end of our study, we obtained PGJ₂ and found that it was as cytotoxic as PGD₂ for L1210 cells but was more lethal for human melanoma cells.

The primary effect of all three PGs was to block cell progression from G₁ to S. At 2.5 µg of PGD₂ per ml, the blockade of cells in G₁ and normal progression through the other phases resulted in accumulation of 80–90% of the cells in G₁. At this dose, there was no inhibition of DNA synthesis, and cells in S progressed apparently normally through S, until all cells were blocked in G₁. DNA synthesis was inhibited at 5 µg/ml which slowed cell progression through S and accumulated cells in G₁. The partial synchronization of cells in G₁ may be useful in devising new combinations of PGD₂ with antitumor drugs.

¹ To whom requests for reprints should be addressed.

Received 7/22/85. Revised 1/ 7/86. Accepted 1/ 7/86.

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