School of Chinese Medicine
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
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. © 2012 The Pharmaceutical Society of Japan.
Alkylphenol, Ardisia brevicaulis, Endoplasmic reticulum stress, Human non-small-cell lung cancer, Myrsinaceae
Source Publication Title
Chemical and Pharmaceutical Bulletin
Pharmaceutical Society of Japan
Link to Publisher's Edition
Zhu, Guo-Yuan, Blenda Chi Kwan Wong, Aiping Lu, Zhao-Xiang Bian, Ge Zhang, Hu-Biao Chen, Yuen Fan Wong, Wang-Fun Fong, and Zhijun Yang. "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." Chemical and Pharmaceutical Bulletin 60.8 (2012): 1029-1036.