TITLE:
Acetylshikonin Inhibits Colorectal Cancer Growth via PI3K/Akt/mTOR Signaling Pathway
AUTHORS:
Yuzhen Zhu, Yu Zhong, Yu Zhou, Yanyan Liu, Qionglin Huang, Zhe Huang, Yongcun Wang, Hua Ye, Xiaobing Zeng, Xuebao Zheng
KEYWORDS:
Arnebia euchroma, Acetylshikonin, Colorectal Cancer, Apoptosis, PI3K/Akt/mTOR Pathway
JOURNAL NAME:
Chinese Medicine,
Vol.9 No.3,
August
8,
2018
ABSTRACT: 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.