Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors: SL142 or SL325 and Retinoic acids

Shaoteng Han, Takuya Fukazawa, Tomoki Yamatsuji, Junji Matsuoka, Hiroyuki Miyachi, Yutaka Maeda, Mary Durbin, Yoshio Naomoto

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RARa, RARb, RXRa and RXRb were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer.

Original languageEnglish
Article numbere13834
JournalPloS one
Volume5
Issue number11
DOIs
Publication statusPublished - Nov 18 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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