The ability of retinoic acid (RA) to inhibit the growth of three cell lines (Te85, Hs781, and Hs791) derived from human osteosarcomas and two cell lines (Hs705 and Hs819) derived from human chondrosarcomas was studied in culture. The exposure to 10-5m RA resulted, within 4 days, in changes in both cell morphology and cell growth. RA-treated cells appeared flat and spread on the substratum more than untreated cells, their exponential growth rates decreased, and their saturation densities were markedly reduced. All these effects could be reversed by removal of RA from the growth medium. The various cell lines exhibited differential susceptibility to the growth-inhibitory effect of RA. The most sensitive was the Hs705 chondrosarcoma. The proliferation of these cells was inhibited 50% by 10-9m RA and was completely blocked by 10-5m RA. In contrast, the concentrations of RA required for 50% inhibition of Hs791, Te85, Hs819, and Hs781 were 10-7, 2 × 10-7, 2.5 × 10-7, and 2 × 10-6m, respectively. Only the Te85 and the Hs781 osteosarcoma cells and cells derived from a chondrosarcoma biopsy were able to form colonies in a semisolid medium, and this growth was dramatically inhibited by RA. These results demonstrate that RA can suppress in these mesenchymal tumor cells the expression of morphological and growth properties frequently associated with transformed cells.


Supported by a grant from the United States-Israel Binational Science Foundation, Jerusalem, Israel.

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