Induction of apoptosis through the up-regulation of endoplasmic reticulum stress sensors by 5-hydroxy-7- (4”-hydroxy-3”-methoxyphenyl)-1-phenyl-3-heptanone

Kisang  Kwon; Kang Kyung-Hee; Seung-Whan  Kim; O-Yu Kwon

doi:10.18388/abp.2020_5709

Kisang Kwon Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan 54538, Korea
Kang Kyung-Hee Department of Dental Hygiene, College of Medical Science, Konyang University, Daejeon 35365, Korea
Seung-Whan Kim Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon 35015, Korea
O-Yu Kwon Department of Anatomy and Cell Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea

DOI: https://doi.org/10.18388/abp.2020_5709

Abstract

The diarylheptanoid, 5-hydroxy-7-(4”-hydroxy-3”-metho-xyphenyl)-1-phenyl-3-heptanone (HPH), is isolated from rhizomes of Alpinia officinarum. There is no reported biological function for this compound other than the inhibition of pancreatic lipase. Cell viability, the expression of endoplasmic reticulum (ER) stress genes, the activation of ER stress sensors, and the induction of apoptosis and autophagy were confirmed following HPH treatment of PC12 cells. No cytotoxicity was observed when the cells were treated with 50 μg/ml HPH, but 40% cell death was observed using MTT assays with 100 μg/ml HPH. Although HPH did not change the expression of the ER chaperones PDI, binding BiP, and calnexin, it upregulated the expression of genes for the ER stress sensors ATF6, eIF2α, and PERK. HPH also induced apoptosis via the activation of ATF6 fragmentation, the phosphorylation of eIF2α, and XBP1 mRNA splicing. Eventually, the results of this study demonstrated that HPH induces apoptosis through upregulation of gene expression of ER stress sensors, which may provide a basis for the development of new drugs using HPH.