Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo
Abstract Background The present study investigated the pharmacological activity and mechanism of ethanol extract of Ligustrum lucidum Ait. leaves (EEL) on HCC. Methods Cell viability was determined using cell counting kit-8 (CCK-8) assay. The effects of EEL on cellular biological activities were ana...
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doaj-e096b58025c7482784e657ac327ba8e82020-11-25T03:47:24ZengBMCCancer Cell International1475-28672019-09-0119111310.1186/s12935-019-0960-5Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivoGuoyan Tian0Jin Chen1Yan Luo2Jin Yang3Tao Gao4Junping Shi5Department of Oncology and Hematology, The Affiliated Hospital of Hangzhou Normal UniversityThe Fourth Clinical Medical College, Zhejiang Chinese Medicine UniversityInstitute of Translational Medicine, The Affiliated Hospital of Hangzhou Normal UniversityInstitute of Translational Medicine, The Affiliated Hospital of Hangzhou Normal UniversityTCM Gynecology, Hangzhou Hospital of Traditional Chinese MedicineDepartment of Liver Diseases, The Affiliated Hospital of Hangzhou Normal UniversityAbstract Background The present study investigated the pharmacological activity and mechanism of ethanol extract of Ligustrum lucidum Ait. leaves (EEL) on HCC. Methods Cell viability was determined using cell counting kit-8 (CCK-8) assay. The effects of EEL on cellular biological activities were analyzed by flow cytometry (FCM), cell wound scratch assay and transwell assay. The expression levels of related mRNA and protein were determined by performing quantitative real-time PCR (qRT-PCR), Western blotting assay and immunocytochemistry. Methylation-specific PCR (MSP) was carried out to investigate the possible mechanism underlying the DNA methylation of PTEN. Results EEL showed cytotoxicity to both Bel-7402 and Huh-7 cell lines. We also found that EEL enhanced the apoptosis of Bel-7402 and Huh-7 cells by regulating the expressions of Bcl-2 associated X (Bax), B cell lymphoma 2 (Bcl-2) and Cytochrome-C and the activity of caspase-3 and therefore promoted cell cycle arrest. Moreover, EEL also suppressed cell migration and invasion. EEL increased the expression of tissue inhibitor of metalloproteinases 2 (TIMP2) but decreased the expressions of matrix metalloproteinase2 (MMP2) and MMP9. Furthermore, EEL inhibited the phosphorylation of PI3K/Akt pathway. MSP results showed that EEL promoted the demethylation of PTEN, suggesting that the inactivation of PI3K/Akt may be related to DNA de-methylation of PTEN. In addition, EEL inhibited the tumor growth of HCC in vivo. Conclusions EEL exerted anti-tumor effect on HCC in vitro and in vivo. EEL mediated by the inhibition of PI3K/Akt may be closely related to DNA de-methylation of PTEN. Thus, EEL could be used as a potential anti-cancer therapeutic agent of HCC.http://link.springer.com/article/10.1186/s12935-019-0960-5Ethanol extract of Ligustrum lucidum Ait. leaves (EEL)Hepatocellular carcinoma (HCC)DNA methylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guoyan Tian Jin Chen Yan Luo Jin Yang Tao Gao Junping Shi |
spellingShingle |
Guoyan Tian Jin Chen Yan Luo Jin Yang Tao Gao Junping Shi Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo Cancer Cell International Ethanol extract of Ligustrum lucidum Ait. leaves (EEL) Hepatocellular carcinoma (HCC) DNA methylation |
author_facet |
Guoyan Tian Jin Chen Yan Luo Jin Yang Tao Gao Junping Shi |
author_sort |
Guoyan Tian |
title |
Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo |
title_short |
Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo |
title_full |
Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo |
title_fullStr |
Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo |
title_full_unstemmed |
Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo |
title_sort |
ethanol extract of ligustrum lucidum ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2019-09-01 |
description |
Abstract Background The present study investigated the pharmacological activity and mechanism of ethanol extract of Ligustrum lucidum Ait. leaves (EEL) on HCC. Methods Cell viability was determined using cell counting kit-8 (CCK-8) assay. The effects of EEL on cellular biological activities were analyzed by flow cytometry (FCM), cell wound scratch assay and transwell assay. The expression levels of related mRNA and protein were determined by performing quantitative real-time PCR (qRT-PCR), Western blotting assay and immunocytochemistry. Methylation-specific PCR (MSP) was carried out to investigate the possible mechanism underlying the DNA methylation of PTEN. Results EEL showed cytotoxicity to both Bel-7402 and Huh-7 cell lines. We also found that EEL enhanced the apoptosis of Bel-7402 and Huh-7 cells by regulating the expressions of Bcl-2 associated X (Bax), B cell lymphoma 2 (Bcl-2) and Cytochrome-C and the activity of caspase-3 and therefore promoted cell cycle arrest. Moreover, EEL also suppressed cell migration and invasion. EEL increased the expression of tissue inhibitor of metalloproteinases 2 (TIMP2) but decreased the expressions of matrix metalloproteinase2 (MMP2) and MMP9. Furthermore, EEL inhibited the phosphorylation of PI3K/Akt pathway. MSP results showed that EEL promoted the demethylation of PTEN, suggesting that the inactivation of PI3K/Akt may be related to DNA de-methylation of PTEN. In addition, EEL inhibited the tumor growth of HCC in vivo. Conclusions EEL exerted anti-tumor effect on HCC in vitro and in vivo. EEL mediated by the inhibition of PI3K/Akt may be closely related to DNA de-methylation of PTEN. Thus, EEL could be used as a potential anti-cancer therapeutic agent of HCC. |
topic |
Ethanol extract of Ligustrum lucidum Ait. leaves (EEL) Hepatocellular carcinoma (HCC) DNA methylation |
url |
http://link.springer.com/article/10.1186/s12935-019-0960-5 |
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