Garcinol from Garcinia indica Downregulates Cancer Stem-like Cell Biomarker ALDH1A1 in Nonsmall Cell Lung Cancer A549 Cells through DDIT3 Activation

Jinhan Wang, Liwen Wang, Chi Tang Ho, Kunsheng Zhang, Qiang Liu, Hui Zhao

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Nonsmall cell lung cancer (NSCLC) is the predominant type of lung cancer. Patients with NSCLC show high mortality rates because of failure to clean up cancer stem cells (CSCs). The anticancer activity of phytochemical garcinol has been identified in various cancer cell models. However, the effect of garcinol on NSCLC cell lines is still lacking. Of the NSCLC cell lines we tested, A549 cells were the most sensitive to garcinol. Interestingly, Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) was preferentially expressed in A549 cells and downregulated by the addition of garcinol. We also found that garcinol enriched DNA damage-inducible transcript 3 (DDIT3) and then altered DDIT3-CCAAT-enhancer-binding proteins beta (C/EBPβ) interaction resulting in a decreased binding of C/EBPβ to the endogenous ALDH1A1 promoter. Furthermore, garcinol's inhibition of ALDH1A1 was identified in a xenograft mice model. Garcinol repressed ALDH1A1 transcription in A549 cells through alterations in the interaction between DDIT3 and C/EBPβ. Garcinol could be a potential dietary phytochemical candidate for NSCLCs patients whose tumors harbored high ALDH1A1 expression.

Original languageAmerican English
Pages (from-to)3675-3683
Number of pages9
JournalJournal of agricultural and food chemistry
Volume65
Issue number18
DOIs
StatePublished - May 10 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Agricultural and Biological Sciences

Keywords

  • A549 cells
  • ALDH1A1
  • garcinol
  • nonsmall cell lung cancer
  • phytochemical

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