Paclitaxel inhibits selenoprotein S expression and attenuates endoplasmic reticulum stress.
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.
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Hong-Shuang
HS
Qin
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Pei-Pei
PP
Yu
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Ying
Y
Sun
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Dan-Feng
DF
Wang
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Xiao-Fen
XF
Deng
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Yong-Li
YL
Bao
Department of Ultrasound, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Jun
J
Song
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Lu-Guo
LG
Sun
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130117, P.R. China.
Zhen-Bo
ZB
Song
Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, P.R. China.
Yu-Xin
YX
Li
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D055808:Drug Discovery / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D051140:Selenoproteins / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins; D017239:Paclitaxel