Physcion inhibits the metastatic potential of human colorectal cancer SW620 cells in vitro by suppressing the transcription factor SOX2

• Published in: Acta pharmacologica Sinica Vol. 37; no. 2; pp. 264 - 275
• Main Authors: Han, Yan-tao, Chen, Xue-hong, Gao, Hui, Ye, Jun-li, Wang, Chun-bo
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.02.2016
• Subjects: AMP-Activated Protein Kinases - metabolism; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Colon - drug effects; Colon - metabolism; Colon - pathology; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Down-Regulation - drug effects; Emodin - analogs & derivatives; Emodin - pharmacology; Epithelial-Mesenchymal Transition - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Glycogen Synthase Kinase 3 beta - metabolism; Humans; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Neoplasm Metastasis - prevention & control; Original; Reactive Oxygen Species - metabolism; Rectum - drug effects; Rectum - metabolism; Rectum - pathology; Signal Transduction - drug effects; SOXB1 Transcription Factors - genetics
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2015.115

Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro. Human colorectal cancer cell line SW620 was tested. Cell migration and invasion were assessed using a wound healing and Transwell assay, respectively. The expression levels of transcription factor SOX2 in the cells were modulated with shRNA targeting SOX2 and SOX2 overexpressing plasmid. The expression of target molecules involved in epithelial-mesenchymal transition (EMT) process and the signaling pathways was determined with Western blots or qRT-PCR. ROS levels were measured using DCF-DA. Physcion (2.5, 5 mol/L) did not affect the cell viability, but dose-dependently inhibited the cell adhesion, migration and invasion. Physcion also inhibited the EMT process in the cells, as evidenced by the increased epithelial marker E-cadherin expression, and by decreased expression of mesenchymal markers N-cadherin, vimentin, fibronectin and α-SMA, as well as transcriptional repressors Snail, Slug and Twist. Physcion suppressed the expression of SOX2, whereas overexpression of SOX2 abrogated the inhibition of physcion on metastatic behaviors. Physcion markedly increased ROS production and phosphorylation of AMPK and GSK3β in the cells, whereas the AMPK inhibitor compound C or the ROS inhibitor NAC abolished the inhibition of physcion on metastatic behaviors. Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3β signaling pathways and suppressing SOX2.