Thymoquinone inhibits the proliferation and invasion of esophageal cancer cells by disrupting the AKT/GSK‐3β/Wnt signaling pathway via PTEN upregulation. (9th September 2020)

• Record Type: Journal Article
• Authors: Ma, Jingjing; Zhang, Yunting; Deng, Huan; Liu, Yinghui; Lei, Xiaofei; He, Pengzhan; Dong, Weiguo
• Is Part Of: Phytotherapy research. Volume 34:Number 12(2020)
• Page Start: 3388
• Page End: 3399
• Publication Date: 2020-09-09
• Subjects: esophageal cancer -- PTEN -- thymoquinone; Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.6795
• Languages: English
• ISSNs: 0951-418X

Abstract

Abstract : Although thymoquinone (TQ) has been reported to exert antitumor activity against various types of human cancers without evident toxicity, limited studies have reported the effects of TQ on esophageal cancer. Here, we showed that TQ induced cell cycle arrest in the G2/M phase and significantly inhibited cell proliferation and invasion. Further investigation of the potential mechanism revealed that TQ increased the levels of p53 and p21 but significantly reduced the expression of Cyclin B1, Cyclin A, and Cyclin E. Moreover, TQ led to a decrease in Bcl‐2 and an increase in cleaved caspase‐3, cleaved caspase‐7, cleaved caspase‐9, and Bax, indicating that TQ induced apoptosis by activating the intrinsic mitochondrial apoptosis pathway. Western blotting showed that TQ disrupted the PI3K/AKT pathway by upregulating PTEN, thus modulating GSK‐3β activity, increasing β‐catenin degradation, and decreasing decreased MMP‐2 and MMP‐9 levels in Eca109 cells. However, these changes were attenuated by disrupting PTEN function (using a potent inhibitor) or downregulating PTEN expression. In addition, in vivo results showed that the efficacy of TQ as an antitumor agent in a mouse xenograft tumor model. In conclusion, TQ suppressed human esophageal cancer cells proliferation and invasion both in vitro and in vivo and could provide a novel therapeutic approach for esophageal cancer.