Alkylphenols from the roots of Ardisia brevicaulis induce G1 arrest and apoptosis through endoplasmic reticulum stress pathway in human non-small-cell lung cancer cells.

Citation data:

Chemical & pharmaceutical bulletin, ISSN: 1347-5223, Vol: 60, Issue: 8, Page: 1029-36

Publication Year:
2012
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Repository URL:
http://repository.hkbu.edu.hk/hkbu_staff_publication/1548
PMID:
22863707
DOI:
10.1248/cpb.c12-00302
Author(s):
Zhu, Guo-Yuan, Wong, Blenda Chi Kwan, Lu, Aiping, Bian, Zhao-Xiang, Zhang, Ge, Chen, Hu-Biao, Wong, Yuen Fan, Fong, Wang-Fun, Yang, Zhijun
Publisher(s):
Pharmaceutical Society of Japan
Tags:
Pharmacology, Toxicology and Pharmaceutics, Chemistry, Alkylphenol, Ardisia brevicaulis, Endoplasmic reticulum stress, Human non-small-cell lung cancer, Myrsinaceae
article description
From the roots of Ardisia brevicaulis DIELS, two new alkylphenol derivatives, named ardisiphenol E (2) and F (3), have been isolated together with a known alkylphenol, ardisiphenol D (1). The structures of 1-3 were elucidated by chemical and spectroscopic techniques. Compounds 1 and 2 exhibited strong cytotoxicities on two human non-small-cell lung cancer cell lines (H1299 and A549). We found that compounds 1 and 2 upregulated mRNA and protein expressions of endoplasmic reticulum (ER) stress markers including C/EBP homologous protein (CHOP), binding immunoglobulin protein (Bip) and inositol-requiring enzyme 1 (IRE1) indicating 1 and 2 are novel natural ER stress inducers. Treatments with 1 and 5 µM of 1 or 2 triggered G1 arrest in H1299 and A549 cells with concomitant downregulation of ubiquitin fusion degradation protein 1 (Ufd1) and S-phase kinase-associated protein 2 (Skp2) proteins and the accumulation of p27, the key axes of ER stress-mediated G1 arrest. Compounds 1 and 2 also induced apoptosis at high concentrations (10, 20 µM) which was shown to be coupled with the upregulation of CHOP and Bim, the activation of caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage. These results indicate that compounds 1 and 2 induce ER stress that subsequently causes G1 arrest and apoptosis in human non-small-cell lung cancer cells and they may have potential anticancer effects.

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