ABSTRACT
The antiproliferative and cytotoxic effects of closely related coumarins, including esculetin, scopoletin and umbelliferone against human T, B lymphoid, myeloid, erythroid and mastocytoma cell lines, were studied in vitro. Esculetin was found to inhibit, dose- dependently, the proliferation of most cell lines. Myeloblastic leukemia, KG-1, was the most sensitive to the effect of esculetin. The Lc 50 was 24.7 micro M. Other cell lines were also susceptible to the effect of esculetin. CEM demonstrated an Lc 50 of 35.2 micro M, and EBV-transformed cell lines demonstrated an Lc 50 of 41.7 and 46.9 micro M. Some cell lines were quite resistant and include T-cell line Ke 37 and the erythroblastic leukemia K562. Interestingly, CTLL16, a crytotoxic normal T-cell line which is dependent on its growth on IL-2, did not show any appreciable cytotoxic effect to esculetin even when the cell had undergone 2 cycles of cell division. Mastocytoma showed in vitro stimulation by esculetin at low concentrations and by scopletin and umbelliferone at high concentrations, in vivo studies indicated that esculetin, scopoletin and umbelliferone were potent inhibitors of bone marrow mitosis. The results were discussed based on available data relating the effects of esculetin on leukotrienes and leukotrienes role in cell growth