The antiproliferative effect of trans-retinoic acid is associated with selective induction of interleukin-1 beta, a cytokine that directly inhibits growth of lung cancer cells.
Retinoids show promise for prevention and treatment of cancers. In most cases, the mechanisms of their anticancer effects are poorly defined, but interactions with cytokine genes have been postulated in several systems. The effects of trans-retinoic acid (RA) on proliferation and cytokine gene expression in the human lung carcinoma Lu-CSF-1 are reported. RA exhibited cell-cycle independent inhibition of Lu-CSF-1 growth while stimulating endogenous interleukin-1 beta and suppressing granulocyte-macrophage colony-stimulating factor and IL-6 mRNAs. Reduction in granulocyte-macrophage colony-stimulating factor and IL-6 message was associated with reduced RNA stability and was translated into reduced protein levels. IL-1 beta mRNA stability was not decreased, and elevation in IL-1 beta protein levels was of a comparable magnitude to the increased amounts of its RNA. Growth inhibition similar to that following RA treatment could be reproduced by exposing cells to exogeneous IL-1 beta alone. These data suggest that changes in autologous cytokine gene expression might contribute to growth inhibition of lung cancer cells by RA.
Ross
H J
HJ
Department of Medicine, University of California Irvine 92697, USA. hross@orion.oac.uci.edu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor