当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > The synthetic chalcone derivative 2-hydroxy-3',5,5'-trimethoxychalcone induces unfolded protein response-mediated apoptosis in A549 lung cancer cells.

The synthetic chalcone derivative 2-hydroxy-3',5,5'-trimethoxychalcone induces unfolded protein response-mediated apoptosis in A549 lung cancer cells.

Abstract：

:The synthetic chalcone derivative 2-hydroxy-3',5,5'-trimenthoxyochalcone (named DK-139) exhibits anti-inflammatory and anti-tumor invasion properties. However, effects of DK-139 on tumor cell growth remain unknown. In the present study, we evaluated the inhibitory activity of DK-139 against human lung cancer cells. Treatment with DK-139 inhibited clonogenicity in various lung cancers and stimulated the caspase cascade, leading to the apoptosis of A549 lung cancer cells. To investigate the mode of action of DK-139-induced apoptosis, we analyzed the effect of DK-139 on the endoplasmic reticulum (ER) stress response. DK-139 increased expression of ER stress sensors, including p-PERK, GRP78/BiP, and IRE1α. IRE1α-regulated XBP-1 mRNA splicing and PERK-induced ATF4 expression was also upregulated following DK-139 treatment. In addition, expression levels of the pro-apoptotic transcription factor CHOP and its downstream target Bim, which is involved in mitochondria-mediated apoptosis, were increased by DK-139 treatment. These results suggest that DK-139 triggers caspase-mediated apoptosis via the ER stress-activated unfolded protein response (UPR) pathway. We propose that the synthetic chalcone derivative DK-139 may be used as a potential agent for the prevention and/or treatment of human lung cancer.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Gil HN,Koh D,Lim Y,Lee YH,Shin SY

doi

10.1016/j.bmcl.2018.07.003

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

2969-2975

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30554-7

journal_volume

28

pub_type

杂志文章

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