期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 65, 期 18, 页码 3675-3683出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.7b00346
关键词
garcinol; ALDH1A1; A549 cells; phytochemical; nonsmall cell lung cancer
资金
- National Natural Science Foundation of China [31571832, 31671873, 31670859]
- Natural Science Foundation of Tianjin [15KPXM01SF056]
- Fundamental Research Funds for CAMS PUMC [2016ZX310068, 2016RC310017]
- Research Funds for the Innovation Team of IRM-CAMS [1650]
- Tianjin Innovative Research Team Grant [TD-12-5049]
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 Al (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/EBP beta) interaction resulting in a decreased binding of C/EBP beta 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/EBP beta. Garcinol could be a potential dietary phytochemical candidate for NSCLCs patients whose tumors harbored high ALDH1A1 expression.
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