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Front. Pharmacol. | doi: 10.3389/fphar.2018.01356

Prevention of Wogonin on Colorectal Cancer Tumorigenesis by Regulating p53 Nuclear Translocation

 Linlin Lu1*,  Qian Feng1, Haojia Wang1, Jiaying Pang1, Liyan Ji1, Jiada Han1, Ying Wang1, Xiaoxiao Qi1 and  Zhong-qiu Liu1*
  • 1Interational Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, China

The tumor suppressor protein p53 plays an important role in the development and progression of colon cancer, and the subcellular organelle localization directly affects its function. Wogonin (5,7-dihydroxy-8-methoxyflavone), a mono-flavonoid extracted from root of Scutellaria baicalensis Georgi, possesses acceptable toxicity and has been used in colorectal cancer chemoprevention in pre-clinical trials by oncologist. However, the underlying anti-colon cancer mechanisms of wogonin are not yet fully understood. In the present study, the effect of wogonin on the initiation and development of colitis-associated cancer through p53 nuclear translocation was explored. AOM-DSS colorectal cancer animal model and human colorectal cancer HCT-116 cell model were used to evaluate the in vivo and in vitro anti-lung cancer action of wogonin. We observed that wogonin showed a dramaticlly preventive effect on colon cancer. Our results showed that wogonin caused apoptotic cell death in human colorectal cancer HCT-116 cell through increased endoplasmic reticulum stress. Meanwhile, excessive endoplasmic reticulum stress facilitated the cytoplasmic localization of p53 through increasing phosphor-p53 at S315 and S376 sites, induced caspase-dependent apoptosis and inhibited autophagy. Furthermore, we verified the chemoprevention effect and toxicity of wogonin in vivo by utilizing an AOM-DSS colon cancer animal model. We found that wogonin not only reduced tumor multiplicity, preserved colon length to normal (6.79 ± 0.34 to 7.41 ± 0.56, P< 0.05) but also didn’t induce side effects on various organs. In conclusion, these results explain the anti-tumor effect of wogonin in colorectal cancer and suggest wogonin as a potential therapeutic candidate for the therapeutic strategy in colorectal cancer treatment.

Keywords: wogonin, colorectal cancer, p53 Nuclear Translocation, Endoplasmic Reticulum Stress, Apoptosis, Autophagy

Received: 17 Sep 2018; Accepted: 05 Nov 2018.

Edited by:

Vincent Kam Wai Wong, Macau University of Science and Technology, Macau

Reviewed by:

Jianxin Chen, Beijing University of Chinese Medicine, China
Songxiao Xu, Artron BioResearch Inc., Canada  

Copyright: © 2018 Lu, Feng, Wang, Pang, Ji, Han, Wang, Qi and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Linlin Lu, Interational Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China,
Prof. Zhong-qiu Liu, Interational Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China,