Combinational treatment with retinoic acid derivatives in non-small cell lung carcinoma in vitro

Jung Choi Eun, Mi Whang Young, Jin Kim Seok, Jin Kim Hyun, Yeul Hong Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The growth inhibitory effects of four retinoic acid (RA) derivatives, 9-cis RA, 13-cis RA, N-(4-hydroxyphenyl) retinamide (4-HPR), and all-trans retinoic acid (ATRA) were compared. In addition, the effects of various combinations of these four agents were examined on non-small cell lung carcinoma (NSCLC) cell-lines, and on the expressions of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) on these cells. At the clinically achievable concentration of 1 μM, only 4-HPR inhibited the growths of H1299 and H460 cells-lines. However, retinoic acid receptor β (RARβ) expression was up-regulated on H460 and H1299 cells treated with 1 μM of ATRA, 13-cis RA, or 9-cis RA. All NSCLC cell lines showed growth inhibition when exposed sequentially to 1 μM ATRA and 0.1 μM 4-HPR. In particular, sequential treatment with 1 μM ATRA or 13-cis RA and 4-HPR markedly inhibited H1703 cell growth; these cells exhibited no basal RARβ expression and were refractory to 4-HPR. However, in NSCLC cell lines that expressed RARβ, the expressional levels of RARβ were up-regulated by ATRA alone and by sequential treatment with ATRA and 4-HPR. 4-HPR was found to be the most active of the four agents in terms of NSCLC growth-inhibition. Moreover, sequential treatments with ATRA or 13-cis RA followed by 4-HPR were found to have synergistic growth-inhibitory effects and to regulate RAR expression.

Original languageEnglish
JournalJournal of Korean Medical Science
Volume22
Issue numberSUPPL.
Publication statusPublished - 2007 Sep 1

    Fingerprint

Keywords

  • Chemoprevention
  • Fenretinide
  • Non-small-cell lung carcinoma
  • Receptors
  • Retinoic acid
  • Retinoids

ASJC Scopus subject areas

  • Medicine(all)

Cite this