Truncated apolipoprotein C-I induces apoptosis in neuroblastoma by activating caspases in the extrinsic and intrinsic pathways

Guo,Fei; Zhao,Wei; Yang,Lin; Yang,Yang; Wang,Saiqi; Wang,Yingjun; Li,Zhaoming; Wang,Jiaxiang

doi:10.3892/or.2017.5819

Truncated apolipoprotein C-I induces apoptosis in neuroblastoma by activating caspases in the extrinsic and intrinsic pathways

Authors:
- Fei Guo
- Wei Zhao
- Lin Yang
- Yang Yang
- Saiqi Wang
- Yingjun Wang
- Zhaoming Li
- Jiaxiang Wang
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Affiliations: Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, College of Pharmacy, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: July 14, 2017 https://doi.org/10.3892/or.2017.5819
Pages: 1797-1805

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Abstract

Truncated apolipoprotein C-I is a post-translationally modified protein characterized by the loss of threonine and proline residues from the N-terminus of the mature peptide. The truncated peptide is involved in many physiological and pathological processes in vivo and is related to malignant diseases. The aim of the present study was to assess the effects of the truncated peptide on tumorigenesis in neuroblastoma. The truncated peptide was chemically synthesized, and a signal peptide was used as the negative control. The results of the CCK-8 assay showed that the truncated peptide selectively inhibited cell proliferation compared with the signal peptide, and inhibited migration and invasion as determined by wound healing and Transwell assays. Flow cytometry analysis demonstrated that the truncated peptide induced apoptosis and cell cycle arrest in the S phase. Bax, Bim, and tBid upregulation, and Bcl‑2 and Bcl‑xl downregulation were associated with permeabilization of the mitochondrial membrane, as detected by the JC-1 assay and the release of cytochrome c and apoptosis. Activation of caspase‑8 was associated with activation of cell death receptors such as the tumor necrosis factor receptor. PARP cleavage indicated apoptosis, and DNA damage was observed in the TUNEL assay. The results showed that the truncated apoC-I induced apoptosis in neuroblastoma by the extrinsic and intrinsic pathways. The anticancer effects were confirmed in vivo in a xenograft mouse model. In conclusion, the endogenous protein apoC-I may be a new promising therapeutic target to suppress tumor growth.

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