Journal
PHARMACEUTICAL BIOLOGY
Volume 56, Issue 1, Pages 528-534Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/13880209.2018.1510974
Keywords
Trace element; antitumor; human liver cancer; oxidative stress; mitochondrial pathway
Funding
- Program for the Top Young Academic Leaders of Higher Learning Institutions of Shanxi
- Fund for Shanxi Key Subjects Construction (FSKSC)
- Collaborative Innovation Center Project of Shanxi 'Astragalus' Resource Industrialization and Industrial Internationalization [HQXTCXZX2016-021]
- Shanxi Province Natural Science Foundation [201601D011112]
- Key Research and Development Program in Shanxi Province of China [201603D21109]
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Context: Selenium nanoparticles (SeNPs) have attracted worldwide attention due to their unique properties and potential bioactivities. Considering that hawthorn is both a traditional medicine and a common edible food, hawthorn fruit extract (HE) was chosen as a reductant to prepare SeNPs. Objective: SeNPs were synthesized by using an aqueous HE as a reductant and stabilizer. The antitumor activities and potential mechanisms of SeNPs were explored by using a series of cellular assays. Materials and methods: The HE mediated SeNPs (HE-SeNPs) were examined using various characterisation methods. The cytotoxicity was measured against HepG2 cells after treated with 0, 5, 10 and 20g/mL of HE-SeNPs for 24h. Annexin V-FITC/PI staining analysis was performed to observe the apoptosis of HepG2 cells. Additionally, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels were evaluated. Finally, the protein expression levels of caspase-9 and Bcl-2 were identified by Western blot. Results: The mono-dispersed and stable SeNPs were prepared with an average size of 113nm. HE-SeNPs showed obvious antitumor activities towards HepG2 cells with an IC50 of 19.225.3g/mL. Results from flow cytometry revealed that both early and total apoptosis rates increased after treating with HE-SeNPs. After cells were treated with various concentrations of HE-SeNPs (5, 10 and 20g/mL) for 24h, the total rate increased to 7.3 +/- 0.5, 9.7 +/- 1.7 and 19.2 +/- 1.6%, respectively. Meanwhile, treatment of HE-SeNPs up-regulated intracellular ROS levels and reduced the MMP. In addition, HE-SeNPs induced the up-regulation of caspase-9 and down-regulation of Bcl-2. Discussion and conclusions: HE-SeNPs induced intracellular oxidative stress and mitochondrial dysfunction to initiate HepG2 cell apoptosis through the mitochondrial pathway. Therefore, HE-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for human liver cancer.
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