EFFECTS OF RETINOIC ACID (ALL-TRANS AND 9-CIS) ON TUMOR PROGRESSION IN SMALL-CELL LUNG-CARCINOMA

The two stereoisomers of retinoic acid (RA), all-trans and 9-cis-RA, a re regulators of cell proliferation, differentiation and apoptosis. In this study, the aim was to evaluate the effects of all-trans-and 9-ci s-RA on cell growth, proliferation, and on the induction of apoptosis in the human small cell lung carcinoma (SCLC) cell lines NCI-H82 and N CI-H209. The application of various concentrations of all-trans and 9- cis-RA were able to inhibit cell growth and proliferation. Moreover, H -3-thymidine incorporation was inhibited and the number of viable cell s decreased, suggesting that all-trans-RA and 9-cis-RA can inhibit cel l proliferation in a dose dependent manner. Morphological examinations (light, electron and fluorescence microscopy) demonstrated that both retinoids had profound effects on the induction of apoptosis. Our inve stigation also showed that, compared to all-trans-RA, 9-cis-RA is a st ronger inducer for the inhibition of cell growth and proliferation and that it is more effective in the induction of apoptosis in small cell lung carcinoma cells in culture. (C) 1998 Academic Press.