Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 79, Issue -, Pages 112-119Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2016.02.003
Keywords
Pristimerin; Colorectal cancer; HCT-116 xenograft; Apoptosis; Metastasis
Funding
- National Natural Science Foundation of China [81274146, 81273604, 81320108029]
- Fundamental Research Funds for the Central Universities [ZD2014YW0032, YD2014SK002]
- 333 high level project of Jiangsu Province [BRA2014245]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Colorectal cancer (CRC) is one of the world's most common cancers with a high mortality rate mainly due to metastasis. Our previous study showed that pristimerin had potent antitumor activities against human CRC cells. In the present study, we further evaluated pristimerin anti-tumor and anti-metastatic properties. MTT assay, Hoechst staining, Annexin V/PI double staining, reactive oxygen species (ROS) measurements were used to assess pristimerin cytotoxicity and apoptotic-inducing effects on HCT-116 cells. Wound healing assay and Transwell assay were used to estimate pristimerin anti-migration and anti-invasion activities on CRC cells. Meanwhile, HCT-116 xenograft model applied for investigating in vivo antitumor activities. Our results showed that pristimerin mediated in vitro HCT-116 cell death, through generation of intracellular ROS and apoptosis induction. Tumor volumes and weights measurements, pathological analysis and Tunnel assay proved that pristimerin inhibited in vivo HCT-116 xenografts growth. Pristimerin was also able to limit CRC invasion and metastasis. It caused downregulation of PI3K/AKT/mTOR pathway and its subsequent downstream p70S6K and E4-BP1 proteins. Collectively, pristimerin exerted both in vitro and in vivo cytotoxic and anti-metastatic effects on HCT-116 cells, suggesting that pristimerin has potential as a new anticancer drug for treatment of colon cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.
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