Paclitaxel inhibits selenoprotein S expression and attenuates endoplasmic reticulum stress.

Abstract:

:The primary effect of the endoplasmic reticulum (ER) stress response or unfolded protein response (UPR) is to reduce the load of unfolded protein and promote survival. However, prolonged and severe ER stress leads to tissue injury and serious diseases. Thus, it is important to identify drugs that can attenuate ER stress for the treatment of diseases. Natural products continue to provide lead compounds for drug discovery and front‑line pharmacotherapy for people worldwide. Previous studies have indicated that selenoprotein S (SelS) is a sensitive and ideal maker of ER stress. In the present study, a firefly luciferase reporter driven by the SelS gene promoter was used to screen for natural compounds capable of attenuating ER stress. From this, paclitaxel (PTX) was identified to efficiently inhibit the promoter activity of the SelS gene, and further results revealed that PTX significantly inhibited the tunicamycin‑induced upregulation of SelS at the mRNA and protein levels in HepG2 and HEK293T cells. In addition, PTX was able to efficiently inhibit the expression of the ER stress marker, glucose‑regulated protein 78, in ER stress, indicating that PTX may reverse ER stress. Taken together, these results suggest that PTX is able to inhibit SelS expression during ER stress and attenuate ER stress.

journal_name

Mol Med Rep

authors

Qin HS,Yu PP,Sun Y,Wang DF,Deng XF,Bao YL,Song J,Sun LG,Song ZB,Li YX

doi

10.3892/mmr.2016.5152

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

5118-24

issue

6

eissn

1791-2997

issn

1791-3004

journal_volume

13

pub_type

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