Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy

Davidone C is a newly discovered flavonoid compound purified from the ethyl acetate-soluble fraction of <i>Sophora davidii</i> (Franch.) Skeels. This study explored the anti-tumor activity of davidone C on hepatocellular carcinoma HepG2 and Bel-7402 cells and its mechanism through MTT me...

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Main Authors: Ping Song, Huiqi Huang, Yuanren Ma, Chaoqun Wu, Xinzhou Yang, Ho-Young Choi
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/17/5219
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author Ping Song
Huiqi Huang
Yuanren Ma
Chaoqun Wu
Xinzhou Yang
Ho-Young Choi
author_facet Ping Song
Huiqi Huang
Yuanren Ma
Chaoqun Wu
Xinzhou Yang
Ho-Young Choi
author_sort Ping Song
collection DOAJ
description Davidone C is a newly discovered flavonoid compound purified from the ethyl acetate-soluble fraction of <i>Sophora davidii</i> (Franch.) Skeels. This study explored the anti-tumor activity of davidone C on hepatocellular carcinoma HepG2 and Bel-7402 cells and its mechanism through MTT method, morphological observation, flow cytometry and Western blotting. The results showed that davidone C significantly inhibited the proliferation of HepG2 and Bel-7402 cells in a time- and dose-dependent manner. The morphological changes of apoptotic cells can be observed under an inverted microscope, such as cell floating, chromosome condensation, apoptotic bodies, and other phenomena. The expressions of Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP increased with the increase of dosage while Bcl-2 decreased, suggesting that the apoptotic mechanism might be related to the mitochondrial apoptotic pathway. Moreover, davidone C administration can down-regulate the expression of Grp78, and simultaneously up-regulate the expression of caspase-7 and caspase-12, indicating that the apoptotic mechanism might be related to the ERS pathway. In addition, davidone C can down-regulate the expression of p62, and simultaneously up-regulate the expression of LC3-I and LC3-II with a quantitative dependence, suggesting that the mechanism of apoptosis may be related to the autophagy signal pathway. All these results showed davidone C has potential effects on hepatocellular carcinoma.
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spelling doaj.art-7d9b0d5529374880bfef96abc7df1a422023-11-22T11:00:53ZengMDPI AGMolecules1420-30492021-08-012617521910.3390/molecules26175219Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and AutophagyPing Song0Huiqi Huang1Yuanren Ma2Chaoqun Wu3Xinzhou Yang4Ho-Young Choi5School of Chemistry and Chemical Engineering, Qinghai University for Nationalities, Xining 810007, ChinaSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, ChinaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaDavidone C is a newly discovered flavonoid compound purified from the ethyl acetate-soluble fraction of <i>Sophora davidii</i> (Franch.) Skeels. This study explored the anti-tumor activity of davidone C on hepatocellular carcinoma HepG2 and Bel-7402 cells and its mechanism through MTT method, morphological observation, flow cytometry and Western blotting. The results showed that davidone C significantly inhibited the proliferation of HepG2 and Bel-7402 cells in a time- and dose-dependent manner. The morphological changes of apoptotic cells can be observed under an inverted microscope, such as cell floating, chromosome condensation, apoptotic bodies, and other phenomena. The expressions of Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP increased with the increase of dosage while Bcl-2 decreased, suggesting that the apoptotic mechanism might be related to the mitochondrial apoptotic pathway. Moreover, davidone C administration can down-regulate the expression of Grp78, and simultaneously up-regulate the expression of caspase-7 and caspase-12, indicating that the apoptotic mechanism might be related to the ERS pathway. In addition, davidone C can down-regulate the expression of p62, and simultaneously up-regulate the expression of LC3-I and LC3-II with a quantitative dependence, suggesting that the mechanism of apoptosis may be related to the autophagy signal pathway. All these results showed davidone C has potential effects on hepatocellular carcinoma.https://www.mdpi.com/1420-3049/26/17/5219davidone C<i>Sophora davidii</i> (Franch.) skeelsanticancerhepatocellular carcinomaapoptosisautophagy
spellingShingle Ping Song
Huiqi Huang
Yuanren Ma
Chaoqun Wu
Xinzhou Yang
Ho-Young Choi
Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy
Molecules
davidone C
<i>Sophora davidii</i> (Franch.) skeels
anticancer
hepatocellular carcinoma
apoptosis
autophagy
title Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy
title_full Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy
title_fullStr Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy
title_full_unstemmed Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy
title_short Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy
title_sort davidone c induces the death of hepatocellular carcinoma cells by promoting apoptosis and autophagy
topic davidone C
<i>Sophora davidii</i> (Franch.) skeels
anticancer
hepatocellular carcinoma
apoptosis
autophagy
url https://www.mdpi.com/1420-3049/26/17/5219
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AT huiqihuang davidonecinducesthedeathofhepatocellularcarcinomacellsbypromotingapoptosisandautophagy
AT yuanrenma davidonecinducesthedeathofhepatocellularcarcinomacellsbypromotingapoptosisandautophagy
AT chaoqunwu davidonecinducesthedeathofhepatocellularcarcinomacellsbypromotingapoptosisandautophagy
AT xinzhouyang davidonecinducesthedeathofhepatocellularcarcinomacellsbypromotingapoptosisandautophagy
AT hoyoungchoi davidonecinducesthedeathofhepatocellularcarcinomacellsbypromotingapoptosisandautophagy