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

Abstract

Aim: 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. Methods: 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. Results: 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. Conclusion: Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3β signaling pathways and suppressing SOX2.

Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and autophagy in human nasopharyngeal carcinoma

“…However, the anti-tumor mechanisms of physcion were recently reported in 2014 by two research groups that found that physcion blocked cell cycle progression and induced apoptosis in human breast cancer cells and cervical carcinoma cells, respectively [27,28] . Recently, studies by Han's group have demonstrated that physcion not only acts as an apoptosis-inducing agent but also potentially suppress the metastasis of colorectal cancer [29,30,43] . Moreover, the modulatory effect of physcion on the metabolic function of tumor cells was also reported in a recent study, which showed that physcion suppressed cancer cell proliferation and tumor growth in nude mouse xenografts by inhibiting 6-phosphogluconate dehydrogenase [44] .…”

“…Apoptosis, defined as type-I programmed cell death (PCD), is considered a major route by which chemotherapeutic agents eradicate cancer cells [30] . Two distinct pathways, caspase-independent and caspase-dependent pathways, have been proposed to account for the apoptotic cell death.…”

“…Physcion has been reported to have a variety of pharmacological properties including laxative, hepatoprotective, anti-inflammatory and anti-microbial activities [22][23][24][25] . Recently, physcion has been found to induce apoptosis [26][27][28][29] , block cell cycle arrest [27] , and suppress metastasis [30] in a variety of human cancer cells. In the present study, our results revealed that physcion suppressed the growth of NPC cells in vitro and in vivo.…”

Tegillarca granosa extract Haishengsu inhibits tumor activity via a mitochondrial‑mediated apoptotic pathway

“…The protein concentration was determined using the bicinchoninic acid assay (Beyotime Biotechnology). Western blotting was performed as previously described (19). Extracted proteins (50 µg) in lysates were separated by 10-12% SDS-PAGE and then transferred electrophoretically onto polyvinylidene difluoride membranes (EMD Millipore, Billerica, MA, USA).…”

Physcion-Matured Dendritic Cells Induce the Differentiation of Th1 Cells

“…Furthermore, anthraquinone derivatives have various biological effects such as anti-cancer [9], anti-inflammatory [10], antibacterial [11], and antiviral effects [12]. Physcion is an anthraquinone derivative and has been shown to induce apoptosis of acute lymphoblastic leukemia [13], human nasopharyngeal carcinoma [14], human colorectal cancer (SW620 cells) [15], and hepatocellular carcinoma cells [16]. Physcion 8-O-β-glucopyranoside reduces the release of pro-inflammatory cytokines by downregulating the expression of Toll-like receptor (TLR) 2 and TLR4, and these down-regulations have been reported to have an anti-septic effect [17].…”