Activity of 9-cis-retinoic acid and receptor-selective retinoids in small cell lung cancer cell lines

Dysregulation of retinoid signaling pathways appears to be an early event i n the pathogenesis of small cell lung cancer (SCLC). We evaluated the activ ity of 9-cis-retinoic acid (9cRA), a pan- receptor agonist, and two synthet ic retinoids, TTNPB and LG100153, which are RAR- and RXR- selective respect ively, against a panel of SCLC cell lines. LG100153 was the most potent age nt with an IC50 < 1.0 mu M in three cell lines. TTNPB had an IC50 < 1.0 mu M in two lines, and 9cRA an IC50 < 1.0 mu M in only one. By fluorescent mic roscopy, LG100153, TTNPB and 9cRA also induced morphologic evidence of apop tosis in three, two and one cell lines, respectively. Although the expressi on of RARs and RXRs varied widely between cell lines, there was no clear co rrelation between the level or pattern of receptor expression and retinoid activity. These data suggest that novel retinoids, especially RXR-selective agents, deserve further evaluation in the treatment of SCLC.