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 in the pathogenesis of small cell lung cancer (SCLC). We evaluated the activity of 9-cis-retinoic acid (9cRA), a pan- receptor agonist, and two synthetic retinoids, TTNPB and LG100153, which are RAR- and RXR- selective, respectively, against a panel of SCLC cell lines. LG100153 was the most potent agent with an IC50 < 1.0 microM in three cell lines. TTNPB had an IC50 < 1.0 microM in two lines, and 9cRA an IC50 < 1.0 microM in only one. By fluorescent microscopy, LG100153, TTNPB and 9cRA also induced morphologic evidence of apoptosis in three, two and one cell lines, respectively. Although the expression of RARs and RXRs varied widely between cell lines, there was no clear correlation 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.
Rosati
R
R
Division of Hematology and Oncology, Wayne State University, Detroit, MI, USA.
Ramnath
N
N
Adil
M R
MR
Ou
X
X
Ali
M A
MA
Heyman
R A
RA
Kalemkerian
G P
GP
D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000633:toxicity*; D001565:Benzoates / Q000494:pharmacology* / Q000633:toxicity*; D018288:Carcinoma, Small Cell; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2; D016259:Genes, myc; D008175:Lung Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000502:physiology*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects / Q000502:physiology*; D014212:Tretinoin / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001565:Benzoates; C116984:LG 100153; D019253:Proto-Oncogene Proteins c-bcl-2; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D000077556:Alitretinoin; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid