Novel Caffeic Acid Phenethyl Ester-Mortalin Antibody Nanoparticles Offer Enhanced Selective Cytotoxicity to Cancer Cells
| Autor: | Zhenya Zhang, Huayue Zhang, Noriyuki Ishii, Sunil C. Kaul, Yoshiyuki Ishida, Yue Yu, Jia Wang, Anissa Nofita Sari, Priyanshu Bhargava, Keiji Terao, Renu Wadhwa, Kangmin Yan, Eijiro Miyako |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
mortalin Cancer Research Cell education lcsh:RC254-282 Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation In vivo medicine Caffeic acid phenethyl ester health care economics and organizations biology enhanced drug delivery lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens CAPE In vitro 030104 developmental biology medicine.anatomical_structure Oncology chemistry Apoptosis 030220 oncology & carcinogenesis internalizing antibody Cancer cell biology.protein Cancer research population characteristics cancer therapy nanoparticles Antibody geographic locations |
| Zdroj: | Cancers, Vol 12, Iss 2370, p 2370 (2020) Cancers Volume 12 Issue 9 |
| ISSN: | 2072-6694 |
| Popis: | Caffeic acid phenethyl ester (CAPE) is a key bioactive ingredient of honeybee propolis and is claimed to have anticancer activity. Since mortalin, a hsp70 chaperone, is enriched in a cancerous cell surface, we recruited a unique cell internalizing anti-mortalin antibody (MotAb) to generate mortalin-targeting CAPE nanoparticles (CAPE-MotAb). Biophysical and biomolecular analyses revealed enhanced anticancer activity of CAPE-MotAb both in in vitro and in vivo assays. We demonstrate that CAPE-MotAb cause a stronger dose-dependent growth arrest/apoptosis of cancer cells through the downregulation of Cyclin D1-CDK4, phospho-Rb, PARP-1, and anti-apoptotic protein Bcl2. Concomitantly, a significant increase in the expression of p53, p21WAF1, and caspase cleavage was obtained only in CAPE-MotAb treated cells. We also demonstrate that CAPE-MotAb caused a remarkably enhanced downregulation of proteins critically involved in cell migration. In vivo tumor growth assays for subcutaneous xenografts in nude mice also revealed a significantly enhanced suppression of tumor growth in the treated group suggesting that these novel CAPE-MotAb nanoparticles may serve as a potent anticancer nanomedicine. |
| Databáze: | OpenAIRE |
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