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2017 ; 8
(47
): 82207-82216
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Kaempferol induces hepatocellular carcinoma cell death via endoplasmic reticulum
stress-CHOP-autophagy signaling pathway
#MMPMID29137257
Guo H
; Lin W
; Zhang X
; Zhang X
; Hu Z
; Li L
; Duan Z
; Zhang J
; Ren F
Oncotarget
2017[Oct]; 8
(47
): 82207-82216
PMID29137257
show ga
Kaempferol is a flavonoid compound that has gained widespread attention due to
its antitumor functions. However, the underlying mechanisms are still not clear.
The present study investigated the effect of kaempferol on hepatocellular
carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a
concentration- and time-dependent manner in HepG2 or Huh7 cells, which was
evidenced by the significant increase of autophagy-related genes. Inhibition of
autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished
kaempferol-induced apoptosis. We further hypothesized that kaempferol can induce
autophagy via endoplasmic reticulum (ER) stress pathway. Indeed, blocking ER
stress by 4-phenyl butyric acid (4-PBA) or knockdown of CCAAT/enhancer-binding
protein homologous protein (CHOP) with siRNA alleviated kaempferol-induced HepG2
or Huh7 cells autophagy; while transfection with plasmid overexpressing CHOP
reversed the effect of 4-PBA on kaempferol-induced autophagy. Our results
demonstrated that kaempferol induced hepatocarcinoma cell death via ER stress and
CHOP-autophagy signaling pathway; kaempferol may be used as a potential
chemopreventive agent for patients with hepatocellular carcinoma.