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The therapeutic use of prostaglandins (PGs) which contain various biological activities and are unstable was successfully achieved. PGs were produced in a large scale according to the Corey method and could be stabilized by the formation of a clathrate compound with cyclodextrin, which enabled the production of marketable form of highly pure PGs. Diligence in the development of native PGs and their structural analogs for human therapy resulted in the following six drugs now being on the market in Japan: PGF2 alpha as the first drug of PGs in the world which induces labor; PGE2 as an orally active labor inducing drug; PGE1 for the treatment of peripheral vascular diseases; gemeprost for therapeutic abortion in the middle-term; ornoprostil, as an oral anti-ulcer agent; limaprost for the treatment of peripheral vascular diseases as an oral agent.

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.