Requirement of RNA and protein synthesis and inhibition by ethylenediaminetetraacetic acid of retinoic acid-induced proteoglycan release in a transplantable rat chondrosarcoma.

In in vitro cultures of prepared pieces of transplantable chondrosarcoma from F344 rats, retinoic acid enhanced the release of proteoglycan, with a lag between 6 and 14 hours. The retinoic acid-induced release of proteoglycan was inhibited in vivo and in vitro by cycloheximide, an inhibitor of protein synthesis, and in vitro by actinomycin D and cordycepin, inhibitors of RNA synthesis. These results suggested that the retinoic acid-induced release of proteoglycan depends on de novo RNA and protein synthesis. The proteoglycan release induced by retinoic acid in vitro was blocked by EDTA but not by other proteinase inhibitors (pepstatin, phenylmethylsulfonyl fluoride, and Trasylol) and was completely restored by Zn2+. The degradation of proteoglycan induced by retinoic acid may depend on newly synthesized metal-dependent proteinases.