A novel cell cycle blocker extracted from Stellera chamaejasme L. inhibits the proliferation of hepatocarcinoma cells

Kan,Xiao-Xi; Li,Qi; Chen,Xi; Wang,Ya-Jie; Li,Yu-Jie; Yang,Qing; Xiao,Hong-Bin; Wang,Zhi-Xin; Chen,Ying; Weng,Xiao-Gang; Cai,Wei-Yan; Zhu,Xiao-Xin

doi:10.3892/or.2016.4742

A novel cell cycle blocker extracted from Stellera chamaejasme L. inhibits the proliferation of hepatocarcinoma cells

Authors:
- Xiao-Xi Kan
- Qi Li
- Xi Chen
- Ya-Jie Wang
- Yu-Jie Li
- Qing Yang
- Hong-Bin Xiao
- Zhi-Xin Wang
- Ying Chen
- Xiao-Gang Weng
- Wei-Yan Cai
- Xiao-Xin Zhu
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Affiliations: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China, Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, P.R. China
Published online on: April 13, 2016 https://doi.org/10.3892/or.2016.4742
Pages: 3480-3488

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Abstract

Currently, liver cancer is the sixth most prevalent cancer and the third most common cause of cancer-related death. However, effective chemotherapeutic drugs with low drug resistance and few side-effects for the clinical treatment of liver cancer are lacking. Therefore, the search for novel drugs to compensate for the defects of existing drugs is urgently needed. Herein, we successfully screened an extract named from Stellera chamaejasme L. (SCL), a historically confimed antitumor plant, through a novel extraction platform. In the present study, we firstly screened the anticancer effect of ESC by the sulforhodamine B (SRB) cell proliferation assay in a wide range of malignant cell lines, including A549, NCI-H157, NCI-H460, SK-HEP-1 and HepG2. With the highest inhibitory rate in hepatocarcinoma cells, we further identified the tumor-suppressive efficacy and the safety of ESC in an H22 hepatocarcinoma xenograft model in vivo. In a mechanistic study, flow cytometry and western blot analysis were performed to evaluate the effects of ESC on the induction of cell apoptosis, intervention of cell cycle distribution and its influence on key G2/M-phase regulators. The results showed that ESC significantly inhibited the cell growth of liver cancer cell lines. Accordingly, the tumor inhibition rate was also increased following ESC administration with little systemic toxicity in H22-transplanted mice. Mechanistically, ESC caused obvious G2/M-phase arrest in both the SK-HEP-1 and HepG2 cell lines without cell apoptosis. Furthermore, cyclin B1 was downregulated, while the phosphorylation level of CDK1 was increased in response to ESC treatment. All these data confirmed that ESC possesses potent anti-proliferative efficacy for hepatocarcinoma through the induction of cyclin-mediated cell cycle arrest. Thus, ESC is a promising candidate for hepatocarcinoma treatment in the future.

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