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Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells

Scutellarein (SCU), a flavone found in the perennial herb Scutellaria baicalensis, is known for a wide range of biological activities. In the present study, we investigated the effects of treatment with SCU flavonoids on inducing apoptosis via the extrinsic pathway in Hep3B cells. SCU treatment sign...

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Autores principales: Ha, Sang Eun, Kim, Seong Min, Lee, Ho Jeong, Vetrivel, Preethi, Venkatarame Gowda Saralamma, Venu, Heo, Jeong Doo, Kim, Eun Hee, Lee, Sang Joon, Kim, Gon Sup
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412708/
https://www.ncbi.nlm.nih.gov/pubmed/30682875
http://dx.doi.org/10.3390/nu11020263
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author Ha, Sang Eun
Kim, Seong Min
Lee, Ho Jeong
Vetrivel, Preethi
Venkatarame Gowda Saralamma, Venu
Heo, Jeong Doo
Kim, Eun Hee
Lee, Sang Joon
Kim, Gon Sup
author_facet Ha, Sang Eun
Kim, Seong Min
Lee, Ho Jeong
Vetrivel, Preethi
Venkatarame Gowda Saralamma, Venu
Heo, Jeong Doo
Kim, Eun Hee
Lee, Sang Joon
Kim, Gon Sup
author_sort Ha, Sang Eun
collection PubMed
description Scutellarein (SCU), a flavone found in the perennial herb Scutellaria baicalensis, is known for a wide range of biological activities. In the present study, we investigated the effects of treatment with SCU flavonoids on inducing apoptosis via the extrinsic pathway in Hep3B cells. SCU treatment significantly inhibited Hep3B cell proliferation and induced G2/M phase cell cycle arrest by inhibiting the expression level of the proteins Cdc25C, cdk1 and Cyclin B1. Allophycocyanin (APC)/Annexin V and propidium iodide (PI) double-staining showed upregulation of apoptotic cell death fraction. We further confirmed apoptosis by 4′-6-diamidino-2-phenylindole (DAPI) fluorescent staining and observed DNA fragmentation with agarose gel electrophoresis. Further, immunoblotting results showed that treatment with SCU showed no changes in Bax and Bcl-xL protein levels. In addition, SCU treatment did not affect the mitochondrial membrane potential (MMP) in Hep3B cells. On the contrary, treatment with SCU increased the expression of Fas and Fas ligand (FasL), which activated cleaved caspase-8, caspase-3, and polymeric adenosine diphosphate ribose (PARP), whereas the expression level of death receptor 4 (DR4) decreased. We confirmed that the proteins expressed upon treatment with SCU were involved in the Fas-mediated pathway of apoptosis in Hep3B cells. Thus, our findings in the current study strongly imply that SCU can be a basic natural source for developing potent anti-cancer agents for hepatocellular carcinoma (HCC) treatment.
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spelling pubmed-64127082019-04-09 Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells Ha, Sang Eun Kim, Seong Min Lee, Ho Jeong Vetrivel, Preethi Venkatarame Gowda Saralamma, Venu Heo, Jeong Doo Kim, Eun Hee Lee, Sang Joon Kim, Gon Sup Nutrients Article Scutellarein (SCU), a flavone found in the perennial herb Scutellaria baicalensis, is known for a wide range of biological activities. In the present study, we investigated the effects of treatment with SCU flavonoids on inducing apoptosis via the extrinsic pathway in Hep3B cells. SCU treatment significantly inhibited Hep3B cell proliferation and induced G2/M phase cell cycle arrest by inhibiting the expression level of the proteins Cdc25C, cdk1 and Cyclin B1. Allophycocyanin (APC)/Annexin V and propidium iodide (PI) double-staining showed upregulation of apoptotic cell death fraction. We further confirmed apoptosis by 4′-6-diamidino-2-phenylindole (DAPI) fluorescent staining and observed DNA fragmentation with agarose gel electrophoresis. Further, immunoblotting results showed that treatment with SCU showed no changes in Bax and Bcl-xL protein levels. In addition, SCU treatment did not affect the mitochondrial membrane potential (MMP) in Hep3B cells. On the contrary, treatment with SCU increased the expression of Fas and Fas ligand (FasL), which activated cleaved caspase-8, caspase-3, and polymeric adenosine diphosphate ribose (PARP), whereas the expression level of death receptor 4 (DR4) decreased. We confirmed that the proteins expressed upon treatment with SCU were involved in the Fas-mediated pathway of apoptosis in Hep3B cells. Thus, our findings in the current study strongly imply that SCU can be a basic natural source for developing potent anti-cancer agents for hepatocellular carcinoma (HCC) treatment. MDPI 2019-01-24 /pmc/articles/PMC6412708/ /pubmed/30682875 http://dx.doi.org/10.3390/nu11020263 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ha, Sang Eun
Kim, Seong Min
Lee, Ho Jeong
Vetrivel, Preethi
Venkatarame Gowda Saralamma, Venu
Heo, Jeong Doo
Kim, Eun Hee
Lee, Sang Joon
Kim, Gon Sup
Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells
title Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells
title_full Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells
title_fullStr Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells
title_full_unstemmed Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells
title_short Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells
title_sort scutellarein induces fas-mediated extrinsic apoptosis and g2/m cell cycle arrest in hep3b hepatocellular carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412708/
https://www.ncbi.nlm.nih.gov/pubmed/30682875
http://dx.doi.org/10.3390/nu11020263
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