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2017 ; 8
(18
): 3707-3717
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Santamarine Inhibits NF-?B and STAT3 Activation and Induces Apoptosis in HepG2
Liver Cancer Cells via Oxidative Stress
#MMPMID29151958
Mehmood T
; Maryam A
; Tian X
; Khan M
; Ma T
J Cancer
2017[]; 8
(18
): 3707-3717
PMID29151958
show ga
Sesquiterpene lactones have long been used in traditional Chinese medicines to
treat inflammatory diseases. Recently, sesquiterpene lactone family compounds
have been recognized as potential anticancer agents. Thus, it is necessary to
explore new sesquiterpene lactones and their antitumor mechanism for cancer
treatments. In the present study, we have explored the potential anti-cancer
activity of a novel sesquiterpene lactone compound "santamarine" (STM) in HepG2
cells. It inhibited proliferation and induced apoptosis dose-dependently with
IC(50) ~ 70 ?M. Induction of apoptosis was found to be linked with increased
reactive oxygen species (ROS) generation, decreased activity of thioredoxin
reductase (TrxR), glutathione (GSH) depletion, mitochondrial membrane potential
(??m) dissipation, Bcl-2 family proteins modulation, cytochrome c release,
caspases-9, -8 and -3 activation and PARP cleavage. Further mechanistic study
demonstrated that STM inhibited the constitutive and TNF-?-induced translocation
of NF-?B into nucleus by decreasing phosphorylation of IkB-?. Moreover, STM
inhibited STAT3 activation by decreasing phosphorylation at tyrosine705. NAC
pretreatment reversed the effect of STM-mediated cell death, NF-?B inhibition and
blockage of STAT3 activity, indicating the involvement of oxidative stress in
STM-mediated anticancer activity. Further studies are needed to explore the exact
molecular mechanism of STM-induced apoptosis to develop it into a lead for
treatment of liver cancer in future.