Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
| Autor: | Yuanyuan Wang, Xianhu Feng, Yumeng Wei, Ling Zhao, Chao Pi, Yi Hou, Shaozhi Fu, Xiaomei Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research lcsh:RC254-282 Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo PI3K/Akt signaling pathway medicine Pharmacology (medical) baicalin PI3K/AKT/mTOR pathway A549 cell medicine.diagnostic_test molecular docking technology Cell growth apoptosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Molecular biology In vitro lung cancer 030104 developmental biology Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Molecular Medicine chiral derivatives Baicalin |
| Zdroj: | Molecular Therapy: Oncolytics, Vol 19, Iss, Pp 67-78 (2020) |
| ISSN: | 2372-7705 |
| DOI: | 10.1016/j.omto.2020.08.018 |
| Popis: | In this study, a pair of chiral baicalin (BA) derivatives were synthesized by combining BA with phenylalanine methyl ester based on molecular docking technology, namely BAD and BAL. Cell cytotoxicity trails showed that the cell growth inhibitory effects of both BAD and BAL were increased by 8- to 12-fold compared with BA on A549 cells. Flow cytometry showed that the apoptotic rates of 50 μg/mL BA, BAD, and BAL to A549 cells for 48 h were 17.94%, 24.32%, and 39.69%, respectively. Western blotting analysis showed that BAD and BAL could promote Bax, caspase-3, and caspase-9 expression and inhibit Bcl-2 expression by inhibiting the expression of p-Akt. The tumor inhibition rates of BA, BAD, and BAL in nude mice of tumor-bearing experiment lasting for 24 days were 35.01%, 53.30%, and 59.35%, respectively. These results in vitro and in vivo showed that BAL had higher antitumor activity than did BAD and BA, which were related to promotion of the apoptosis of tumor cells by inhibiting the expression of p-Akt on PI3K/Akt pathway. This study provides an experimental basis for the development of a new configuration of BA for the treatment of cancer. |
| Databáze: | OpenAIRE |
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