[An experimental study on antitumor effect of prostaglandin D2].
The cell growth inhibitory effects of prostaglandin D2 (PGD2) were examined on cultured and implanted malignant tumor cell lines. The results were as follows. 1) PGD2 showed significant cytotoxicity against Sarcoma-180, Ehrlich cancer, Yoshida sarcoma and KATO-III in culture. The cytotoxicity of PGD2 against KATO-III was the lowest. 2) PGD2 at a dose of 40 micrograms/mouse/day was intraperitoneally injected into ddY mice for 10 days starting on the first day after an intraperitoneal implant of 2 X 10(5) Sarcoma-180 cells. As a result, the duration of survival was significantly prolonged. However, intravenous injection was less effective than intraperitoneal injection. 3) Addition of Forskolin to the cultured KATO-III cells with PGD2 resulted in a significant increase of cyclic AMP (cAMP) levels. However, the growth inhibition of PGD2 was independent of elevated levels of cAMP. 4) DNA histograms using flow cytometry showed PGD2 blocked significantly G2 + M phase DNA synthesis in the cultured Sarcoma-180 cells, and S phase DNA synthesis in KATO-III cells was significantly blocked with PGD2 at a concentration of 100 micrograms/ml. The results indicate that PGD2 possesses an antitumor effect on 4 malignant tumor cell lines. Furthermore, it seems that the antitumor mechanism of PGD2 is due to the inhibition of DNA synthesis rather than the action through cAMP-receptor, and the blockade to cell cycle progression is dependent on kinds of tumor cell lines.
Ehara
H
H
Second Department of Surgery, Yokohama City University School of Medicine, Japan.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D066298:In Vitro Techniques; D051379:Mice; D009368:Neoplasm Transplantation; D015230:Prostaglandin D2 / Q000494:pharmacology* / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D015230:Prostaglandin D2