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Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal Transition Associated Transcription Factors Twist1 and Zeb1

1
Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
2
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China
3
Department of Biochemistry, School of Life Sciences, Central South University, Changsha 410013, China
4
Medical College, Hunan Normal University, Changsha 410081, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2017, 22(12), 2105; https://doi.org/10.3390/molecules22122105
Received: 11 October 2017 / Revised: 27 November 2017 / Accepted: 28 November 2017 / Published: 4 December 2017
(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)
Cervical cancer is one of the most common gynecological malignant tumors worldwide, for which chemotherapeutic strategies are limited due to their non-specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ) has been reported to target a vast number of signaling pathways in carcinogenesis in different cancers, and hence is regarded as a promising anticancer molecule. Inhibition of epithelial to mesenchymal transition (EMT) regulators is an important approach in anticancer research. In this study, TQ was used to treat the cervical cancer cell lines SiHa and CaSki to investigate its effects on EMT-regulatory proteins and cancer metastasis. Our results showed that TQ has time-dependent and dose-dependent cytotoxic effects, and it also inhibits the migration and invasion processes in different cervical cancer cells. At the molecular level, TQ treatment inhibited the expression of Twist1, Zeb1 expression, and increased E-Cadherin expression. Luciferase reporter assay showed that TQ decreases the Twist1 and Zeb1 promoter activities respectively, indicating that Twist1 and Zeb1 might be the direct target of TQ. TQ also increased cellular apoptosis in some extent, but apoptotic genes/proteins we tested were not significant affected. We conclude that TQ inhibits the migration and invasion of cervical cancer cells, probably via Twist1/E-Cadherin/EMT or/and Zeb1/E-Cadherin/EMT, among other signaling pathways. View Full-Text
Keywords: thymoquinone; cervical cancer; metastasis; epithelial to mesenchymal transition; Twist1; Zeb1; E-Cadherin thymoquinone; cervical cancer; metastasis; epithelial to mesenchymal transition; Twist1; Zeb1; E-Cadherin
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Li, J.; Khan, M.A.; Wei, C.; Cheng, J.; Chen, H.; Yang, L.; Ijaz, I.; Fu, J. Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal Transition Associated Transcription Factors Twist1 and Zeb1. Molecules 2017, 22, 2105.

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