Pterostilbene Nanoparticles Downregulate Hypoxia-Inducible Factors in Hepatoma Cells Under Hypoxic Conditions
| Autor: | Wei-Lin Teng, Yow-Ling Shiue, Pao-Hsien Huang, Wen-Sheng Tzeng, Feng-Lin Yen, Tzu-Ching Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pterostilbene
Proton Magnetic Resonance Spectroscopy Pharmaceutical Science Apoptosis 02 engineering and technology Pharmacology 01 natural sciences chemistry.chemical_compound International Journal of Nanomedicine Drug Discovery Spectroscopy Fourier Transform Infrared Stilbenes Cytotoxic T cell Original Research Liver Neoplasms General Medicine Hep G2 Cells hepatocellular carcinoma 021001 nanoscience & nanotechnology Cell Hypoxia Hypoxia-inducible factors Hepatocellular carcinoma medicine.symptom 0210 nano-technology Crystallization transcatheter arterial chemoembolization Carcinoma Hepatocellular Cell Survival Biophysics Down-Regulation Bioengineering Antineoplastic Agents 010402 general chemistry Biomaterials Downregulation and upregulation medicine Humans Neoplasm Invasiveness Viability assay Particle Size hypoxia Organic Chemistry Hydrogen Bonding Hypoxia (medical) medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit 0104 chemical sciences Drug Liberation chemistry Solubility Nanoparticles Tumor Hypoxia |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Wen-Sheng Tzeng,1,2 Wei-Lin Teng,3 Pao-Hsien Huang,4 Tzu-Ching Lin,3 Feng-Lin Yen,2,5– 7 Yow-Ling Shiue2 1Department of Radiology, Pingtung Christian Hospital, Pingtung, Taiwan; 2Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 3Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCorrespondence: Feng-Lin YenDepartment of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, No.100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung City, 80708, TaiwanTel +886 7 3121101 ext 2028Email flyen@cc.kmu.edu.twYow-Ling ShiueInstitute of Biomedical Sciences, National Sun Yat-Sen University, No 70 Lien-Hai Road., Kaohsiung City, 80424, TaiwanTel +886 7 5252000 ext 5818Email shirley@imst.nsysu.edu.twPurpose: Transcatheter arterial chemoembolization (TACE) is a common clinical treatment for hepatocellular carcinoma (HCC). However, hypoxia induction after treatment might trigger tumor invasiveness and metastasis. Although pterostilbene (PTS) has antitumor effects, its chemoprevention in HepG2 cells under hypoxia has not been investigated yet. In addition, the poor water solubility of raw PTS limits its clinical application. Here, we prepared nanoparticles of PTS (PSN) and compared their antihepatoma activities with those of raw PTS in HepG2 under hypoxic conditions.Materials and Methods: The PTS nanoparticle formulation was prepared by nanoprecipitation, using Eudragit® e100 (EE) and polyvinyl alcohol (PVA) as carriers. We analyzed the physicochemical properties of raw PTS and PSN, including yield, encapsulation efficiency, water-solubility, particle size, morphology, crystalline-to-amorphous transformation, and molecular interaction between PTS and carriers. We also evaluated their antihepatoma activities under hypoxia treatment in HepG2 cells, including cell viability, hypoxia, and apoptosis.Results: The yield and encapsulation efficiency of PSN were 86.33% and > 99%, respectively. The water solubility and drug release of PTS were effectively improved after nanoprecipitation corresponding to the reduction in particle size, amorphous transformation, and formation of hydrogen bonding with carriers. PSN had a better cytotoxic effect than raw PTS in HepG2 under pre- and post-hypoxia conditions. In addition, hypoxia- and apoptosis-related proteins in HepG2 cells under two different hypoxic conditions were significantly inhibited by PSN compared with the control group with hypoxia only, except for HIF-1α in the post-hypoxia group. PSN was also significantly better in inhibiting these proteins, except for Bcl2, under pre-hypoxic conditions.Conclusion: Our results suggested that PSN could improve the water solubility and drug release of PTS and enhance the efficacy of HCC treatment under hypoxic conditions.Keywords: hepatocellular carcinoma, hypoxia, transcatheter arterial chemoembolization |
| Databáze: | OpenAIRE |
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