The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro

Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and preventio n remains obscure. In this study cytostatic activity of a novel 9-cis-retin oic acid (9-cis-RA) was compared with two other retinoids: tretinoin and is otretinoin, in three different bladder cancer cell lines: RT4 (well differe ntiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 mu g /ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cy tostatic effect was estimated by using luminometric measuring of ATP activi ty of viable cells in suspension. Compared with the older retinoids, tretin oin and isotretinoin, the highest concentration of 9-cis-RA had a cytostati c efficacy in all three bladder cancer cell lines tested. A clear dose-resp onse relationship was observed in isotretinoin-treated cultures after 6 day s and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclud e, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cance r cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be co nsidered when planning clinical trials.