Author(s)

Yuzhen Zhu^1*, Yu Zhong^2*, Yu Zhou³, Yanyan Liu⁴, Qionglin Huang², Zhe Huang⁵, Yongcun Wang⁶, Hua Ye¹, Xiaobing Zeng^1,7*, Xuebao Zheng^1,8*

¹Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, China.
²Analysis Center of Guangdong Medical University, Zhanjiang, China.
³Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁴Department of Clinical Laboratory, Affiliated Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁵Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁶Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁷Center Lab of Longhua Branch, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, China.
⁸Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Acetylshikonin, a major constituent isolated from Arnebia euchroma, is a potential candidate for anti-colorectal cancer drugs. However, the potential activity and underlying mechanism of Acetylshikonin against colorectal cancer remain unclear. Methods: In this study, Acetylshikonin was isolated from the active CHCl3 extract of Arnebia euchroma using activity-guided screening, and elucidated by the extensive spectroscopic analysis and comparison with literature data. Human colorectal cancer cells HT29, DLD-1, HCT116 or Caco-2 were exposed to different concentrations of Acetylshikonin (6.25 - 100 μg/mL) for 24 or 48 h. Cell viability, cell apoptosis and cell cycle distribution were detected. The activity of Acetylshikonin and potential mechanism of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway were evaluated in vitro and vivo. Results: We found that Acetylshikonin exhibited remarkable anti-proliferative activity in a dose-dependent manner against HT29 cells with the IC50 values of 60.82 μg/ml and 30.78 μg/ml at 24, 48 h, respectively. Moreover, Acetylshikonin induced cell cycle arrest at G0/G1 phase and early apoptosis through inhibition of PI3K/Akt/mTOR pathway. Furthermore, the assays of cell inhibition, early apoptosis and G0/G1 phase distribution showed that suppression of the PI3K/Akt pathway using LY294002 enhanced the anti-cancer effect of Acetylshikonin. Similarly, Acetylshikonin also decreased the growth of tumour in colorectal cancer xenografts in mice through PI3K/Akt/mTOR pathway. Conclusions: To sum up, these new findings provided a framework for further exploration of Acetylshikonin which possessed the potential antitumor activity by inhibiting PI3K/Akt/mTOR pathway.

Arnebia euchroma, Acetylshikonin, Colorectal Cancer, Apoptosis, PI3K/Akt/mTOR Pathway

Zhu, Y. , Zhong, Y. , Zhou, Y. , Liu, Y. , Huang, Q. , Huang, Z. , Wang, Y. , Ye, H. , Zeng, X. and Zheng, X. (2018) Acetylshikonin Inhibits Colorectal Cancer Growth via PI3K/Akt/mTOR Signaling Pathway. Chinese Medicine, 9, 126-143. doi: 10.4236/cm.2018.93008.