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[Development of antineoplastic prostaglandins].

Abstract
Prostaglandins (PGs) are bioregulatory substances and are widely distributed in a variety of tissues. Numerous facts have been described in relation to cancer biology with PGs. The purpose of our study lies in the creation of anti-tumor PGs. We have described that PGD2 has strong cell growth inhibitory activity; furthermore, we discovered that PGJ2, 9-deoxy-delta 9-PGD2, has 3 times stronger activity than the mother compound, PGD2. In vivo experiments showed that only PGA2 and PGJ2 exert antitumor activity. Thus, cyclopentenone ring structure in PG seems to be an essential moiety for cytotoxicity of PG. On the basis of the above facts, we propose tha name of antineoplastic PGs for PGA and PGJ derivatives which have cyclopentenone ring. Recently, we developed several antineoplastic PGs which showed IC50 value less than 0.3 microgram/ml against L1210 leukemia cells, and these compounds also showed antitumor activity against Ehrlich ascites tumor in vivo comparable to that of cyclophosphamide. The action mechanism seems to be in its alkylation activity of the cyclopentenone structure and not in receptor-cAMP route. Spectrum of anti-tumor activity and its toxicity in vivo are now under investigation. In this brief review, mainly our recent approaches in this field are discussed.
AuthorsM Fukushima
JournalGan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 10 Issue 9 Pg. 1930-5 (Sep 1983) ISSN: 0385-0684 [Print] JAPAN
PMID6577812 (Publication Type: English Abstract, Journal Article)
Chemical References
  • Antineoplastic Agents
  • Prostaglandins
  • Prostaglandins A
  • Prostaglandins D
  • Prostaglandins E
  • prostaglandin A2
  • Dinoprostone
  • Prostaglandin D2
Topics
  • Antineoplastic Agents
  • Dinoprostone
  • Humans
  • Prostaglandin D2
  • Prostaglandins (blood, chemical synthesis, pharmacology, physiology)
  • Prostaglandins A (pharmacology)
  • Prostaglandins D (pharmacology)
  • Prostaglandins E (pharmacology)

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