Tetrandrine induces G1/S cell cycle arrest through the ROS/Akt pathway in EOMA cells and inhibits angiogenesis in vivo

Xiao,Wenkai; Jiang,Yajie; Men,Qiuxu; Yuan,Ling; Huang,Zebo; Liu,Ting; Li,Wenhua; Liu,Xin

doi:10.3892/ijo.2014.2735

Tetrandrine induces G1/S cell cycle arrest through the ROS/Akt pathway in EOMA cells and inhibits angiogenesis in vivo

Authors:
- Wenkai Xiao
- Yajie Jiang
- Qiuxu Men
- Ling Yuan
- Zebo Huang
- Ting Liu
- Wenhua Li
- Xin Liu
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Affiliations: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China, School of Life Science, Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: October 29, 2014 https://doi.org/10.3892/ijo.2014.2735
Pages: 360-368

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Abstract

Tetrandrine, a bisbenzylisoquinoline alkaloid, is known to inhibit tumor cell proliferation and induce apoptosis in cancer models in vitro and in vivo. In the present study, tetrandrine significantly inhibited the proliferation of mouse endothelial cells (EOMA cell) and induced G1/S arrest in EOMA cells, in which the expressions of cyclin D and cyclin E and CDKs were downregulated. Tetrandrine treatment also caused intracellular accumulation of reactive oxygen species (ROS). Pretreatment with NAC, which is a ROS inhibitor, blocked G1/S cell arrest and cyclin regulation induced by tetrandrine, implying that ROS generation plays an important role in tetrandrine-induced cell cycle arrest. Furthermore, a decreased phospho-Akt protein level after tetrandrine treatment was reversible with the removal of the intracellular ROS by NAC. Notably, overexpression of Akt decreased tetrandrine-induced G1/S arrest. Finally, we verified the antiangiogenic effects of tetrandrine in vivo in a liver cancer xenograft model in nude mice. In conclusion, tetrandrine inhibits EOMA cell growth through the ROS/Akt pathway, and it could be a promising compound for cancer therapy as an inhibitor of tumor vascular growth.

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