Chunhui Nie1,2, Bei Wang1,2, Baoquan Wang1,2, Ning Lv3, Rui Yu4, Enfan Zhang5. 1. Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 2. Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China. 3. Department of Pharmacy, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 4. Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, No. 818, Fenghua Road, Ningbo, Zhejiang, China. yurui@nbu.edu.cn. 5. Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, Zhejiang, China. efzhang@zju.edu.cn.
Abstract
BACKGROUND: Protopine is an isoquinoline alkaloid that possesses various biological activities including the anti-tumour activity. However, the effects of protopine on liver carcinoma cells are still elusive. The aim of this study is to examine the effects of protopine on liver carcinoma cells both in vitro and in vivo. METHODS: MTT assay was performed to measure the cell viability. Wound healing and transwell assays were conducted to assess the motility of cells. Cellular apoptosis and ROS levels were measured by the flow cytometry. Western blotting assay was used to measure the change of proteins. The cytotoxicity of protopine was also evaluated in xenograft mice. RESULTS: Protopine inhibited viabilities and triggered apoptosis via the intrinsic pathway in a caspase-dependent manner in liver carcinoma cells. Furthermore, protopine also induced accumulation of intracellular ROS which further led to the inhibition of PI3K/Akt signalling pathway. Finally, in vivo study showed that protopine also repressed tumour growth in xenograft mice without noticeable toxicity. CONCLUSIONS: Protopine might be used as a potential therapeutic agent for the treatment of liver carcinoma.
BACKGROUND:Protopine is an isoquinoline alkaloid that possesses various biological activities including the anti-tumour activity. However, the effects of protopine on liver carcinoma cells are still elusive. The aim of this study is to examine the effects of protopine on liver carcinoma cells both in vitro and in vivo. METHODS:MTT assay was performed to measure the cell viability. Wound healing and transwell assays were conducted to assess the motility of cells. Cellular apoptosis and ROS levels were measured by the flow cytometry. Western blotting assay was used to measure the change of proteins. The cytotoxicity of protopine was also evaluated in xenograft mice. RESULTS:Protopine inhibited viabilities and triggered apoptosis via the intrinsic pathway in a caspase-dependent manner in liver carcinoma cells. Furthermore, protopine also induced accumulation of intracellular ROS which further led to the inhibition of PI3K/Akt signalling pathway. Finally, in vivo study showed that protopine also repressed tumour growth in xenograft mice without noticeable toxicity. CONCLUSIONS:Protopine might be used as a potential therapeutic agent for the treatment of liver carcinoma.