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Thymoquinone Induces Apoptosis of Human Epidermoid Carcinoma A431 Cells Through ROS-mediated Suppression of STAT3

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Author(s)
Ji Eun ParkDo-Hee KimEunyoung HaSeung Mi ChoiJoon-Seok ChoiKyung-Soo ChunSang Hoon Joo
Keimyung Author(s)
Ha, Eun Young
Department
Dept. of Biochemistry (생화학)
Journal Title
Chemico-biological interactions
Issued Date
2019
Volume
312
Keyword
ThymoquinoneApoptosisROSSTAT3Skin cancer
Abstract
Black seed (Nigella sativa) oil has been used in various dermatological applications, and its major constituent, thymoquinone (TQ) has been shown to exhibit antiproliferative activity against various cancer cells. In this study, we tried to provide a mechanistic basis of apoptosis induced by TQ. Skin squamous carcinoma A431 cells were treated with TQ to monitor the apoptosis induced by TQ. Western blot analysis was performed to detect expression of apoptotic or anti-apoptotic proteins. Cell viability and apoptosis were measured by using the MTT test and FACS analysis, respectively. The induction of intracellular reactive oxygen species (ROS) by TQ was evaluated by 2',7'-dichlorofluorescein diacetate staining. In vivo xenograft study was followed to confirm the antiproliferative effect of TQ. Treatment of A431 cells with TQ-induced apoptosis, which was associated with the induction of p53 and Bax, inhibition of Mdm2, Bcl-2, and Bcl-xl expression, and activation of caspase-9, -7, and -3. TQ inhibited the constitutive phosphorylation and DNA binding activity of signal transducer and activator of transcription-3 (STAT3) in A431 cells by blocking the phosphorylation of the upstream kinase, Src. Moreover, the expression of STAT3 target gene products, cyclin D1 and survivin, was attenuated by TQ treatment. The generation of ROS was increased during TQ-induced apoptosis, and the pretreatment of N-acetyl cysteine, a ROS scavenger, reversed the apoptotic effect of TQ. In vivo study with NOD scid gamma (NSG) mice confirmed the inhibitory effect of TQ on the growth of A431 cells. Our results provide the first demonstration that TQ induces the apoptosis of A431 cells through generation of ROS and inhibition of STAT3 signaling.
Keimyung Author(s)(Kor)
하은영
Publisher
School of Medicine (의과대학)
Citation
Ji Eun Park et al. (2019). Thymoquinone Induces Apoptosis of Human Epidermoid Carcinoma A431 Cells Through ROS-mediated Suppression of STAT3. Chemico-biological interactions, 312, 108799–108799. doi: 10.1016/j.cbi.2019.108799
Type
Article
ISSN
1872-7786
Source
https://www.sciencedirect.com/science/article/abs/pii/S0009279719302765?via%3Dihub
DOI
10.1016/j.cbi.2019.108799
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/42328
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
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