Cargando…

Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hou, Yi, Pi, Chao, Feng, Xianhu, Wang, Yuanyuan, Fu, Shaozhi, Zhang, Xiaomei, Zhao, Ling, Wei, Yumeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533372/
https://www.ncbi.nlm.nih.gov/pubmed/33072864
http://dx.doi.org/10.1016/j.omto.2020.08.018
_version_ 1783590118319194112
author Hou, Yi
Pi, Chao
Feng, Xianhu
Wang, Yuanyuan
Fu, Shaozhi
Zhang, Xiaomei
Zhao, Ling
Wei, Yumeng
author_facet Hou, Yi
Pi, Chao
Feng, Xianhu
Wang, Yuanyuan
Fu, Shaozhi
Zhang, Xiaomei
Zhao, Ling
Wei, Yumeng
author_sort Hou, Yi
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7533372
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher American Society of Gene & Cell Therapy
record_format MEDLINE/PubMed
spelling pubmed-75333722020-10-16 Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway Hou, Yi Pi, Chao Feng, Xianhu Wang, Yuanyuan Fu, Shaozhi Zhang, Xiaomei Zhao, Ling Wei, Yumeng Mol Ther Oncolytics Original Article 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. American Society of Gene & Cell Therapy 2020-09-01 /pmc/articles/PMC7533372/ /pubmed/33072864 http://dx.doi.org/10.1016/j.omto.2020.08.018 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Hou, Yi
Pi, Chao
Feng, Xianhu
Wang, Yuanyuan
Fu, Shaozhi
Zhang, Xiaomei
Zhao, Ling
Wei, Yumeng
Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
title Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
title_full Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
title_fullStr Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
title_full_unstemmed Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
title_short Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
title_sort antitumor activity in vivo and vitro of new chiral derivatives of baicalin and induced apoptosis via the pi3k/akt signaling pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533372/
https://www.ncbi.nlm.nih.gov/pubmed/33072864
http://dx.doi.org/10.1016/j.omto.2020.08.018
work_keys_str_mv AT houyi antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway
AT pichao antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway
AT fengxianhu antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway
AT wangyuanyuan antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway
AT fushaozhi antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway
AT zhangxiaomei antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway
AT zhaoling antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway
AT weiyumeng antitumoractivityinvivoandvitroofnewchiralderivativesofbaicalinandinducedapoptosisviathepi3kaktsignalingpathway