Cell cycle effects of prostaglandins A1, A2, and D2 in human and murine melanoma cells in culture.
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 (RPMI7932,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 micrograms 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 micrograms/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.
Bhuyan
B K
BK
Adams
E G
EG
Badiner
G J
GJ
Li
L H
LH
Barden
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D015230:Prostaglandin D2; D011454:Prostaglandins A / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011454:Prostaglandins A; D011457:Prostaglandins D; D012334:RNA, Neoplasm; D015230:Prostaglandin D2; C100573:prostaglandin A1