Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and autophagy in human nasopharyngeal carcinoma
Authors: Xing-Lin Zhang
Hong-Ying Zhang
Zhun Yang
Ming-Jie Pang
Jun Fan
Zhao-Fang Liu
Journal: Acta Pharmacologica Sinica (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Physcion; apoptosis; autophagy; nasopharyngeal carcinoma; Sp1
Affiliations: Department of Otolaryngology, Qingdao Municipal Hospital, Qingdao 266011, China., Department of Oncology, Qingdao Municipal Hospital, Qingdao 266011, China., Department of Dermatology, Qingdao Municipal Hospital, Qingdao 266011, China.

Abstract:  Aim: Physcion is a major bioactive ingredient in the traditional Chinese medicine Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits a variety of pharmacological activities including laxative, hepatoprotective, anti-inflammatory, anti-microbial and anti-proliferative effects. In this study we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro and in vivo, as well as the mechanisms underlying the anti-tumor action. Methods: The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell viability was detected using MTT and colony formation assays. Flow cytometry was used to assess the cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation. Apoptotic cell death was also confirmed by a TUNEL assay. The expression of target or marker molecules was determined using Western blotting. The activity of caspase-3, 8, and 9 was detected with an ELISA kit. A xenograft murine model was used to evaluate the in vivo anti-tumor action of physcion, the mice were administered physcion (10, 20 mg·kg-1·d-1, ip) for 30 d. Results: Treatment with physcion (5, 10, and 20 μmol/L) dose-dependently suppressed the cell viability and colony formation in CNE2 cells. Physcion (10 and 20 μmol/L) dose-dependently blocked cell cycle progression at G1 phase and induced both caspase-dependent apoptosis and autophagy in CNE2 cells. Furthermore, physcion treatment induced excessive ROS generation in CNE2 cells, and subsequently disrupted the miR-27a/ZBTB10 axis, resulting in repression of the transcription factor Sp1 that was involved in physcion-induced apoptosis and autophagy. Moreover, physcion-induced autophagy acted as a pro-apoptotic factor, and possibly contributed to physcion-induced apoptosis. In the xenograft murine model, administration of physcion dose-dependently suppressed the tumor growth without affecting the body weight. Furthermore, the anti-tumor effects of physcion were correlated with downregulation of Sp1 and suppression of miR-27a in the tumor tissues. Conclusion: Physcion induces apoptosis and autophagy in human nasopharyngeal carcinoma by targeting Sp1, which was mediated by ROS/miR-27a/ZBTB10 signaling. The results suggest that physcion is a promising candidate for the treatment of human nasopharyngeal carcinoma. 

Retracted: No

PubPeer comments:
 There appears to be an error in Fig 6B, where two of the flow-cytometry plots are the same. Could the authors check? ![file] A greater cause for concern is the fact that the  NAC + Physcion panel of 6B also appeared as the  Physcion 10 u03bcmol L panel of Fig 4B. ![file] The corresponding author (Zhun Yang) made an unusual choice of e-mail address for academic correspondence. ![file] ,