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 <i>Scutellaria baicalensis</i>, 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....
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doaj-c0513473aee440a08ea4d15694f00dc02020-11-25T01:14:09ZengMDPI AGNutrients2072-66432019-01-0111226310.3390/nu11020263nu11020263Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma CellsSang Eun Ha0Seong Min Kim1Ho Jeong Lee2Preethi Vetrivel3Venu Venkatarame Gowda Saralamma4Jeong Doo Heo5Eun Hee Kim6Sang Joon Lee7Gon Sup Kim8Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaGyeongnam Department of Environment Toxicology and Chemistry, Biological Resources Research Group, Korea Institute of Toxicology, 17 Jegok-gil, Jinju 52834, KoreaResearch Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaGyeongnam Department of Environment Toxicology and Chemistry, Biological Resources Research Group, Korea Institute of Toxicology, 17 Jegok-gil, Jinju 52834, KoreaDepartment of Nursing Science, International University of Korea, Jinju 52833, KoreaGyeongnam Department of Environment Toxicology and Chemistry, Biological Resources Research Group, Korea Institute of Toxicology, 17 Jegok-gil, Jinju 52834, KoreaResearch Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaScutellarein (SCU), a flavone found in the perennial herb <i>Scutellaria baicalensis</i>, 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.https://www.mdpi.com/2072-6643/11/2/263scutellareinflavonoidhepatocellular carcinomaapoptosiscell cycle arrest |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sang Eun Ha Seong Min Kim Ho Jeong Lee Preethi Vetrivel Venu Venkatarame Gowda Saralamma Jeong Doo Heo Eun Hee Kim Sang Joon Lee Gon Sup Kim |
spellingShingle |
Sang Eun Ha Seong Min Kim Ho Jeong Lee Preethi Vetrivel Venu Venkatarame Gowda Saralamma Jeong Doo Heo Eun Hee Kim Sang Joon Lee Gon Sup Kim Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells Nutrients scutellarein flavonoid hepatocellular carcinoma apoptosis cell cycle arrest |
author_facet |
Sang Eun Ha Seong Min Kim Ho Jeong Lee Preethi Vetrivel Venu Venkatarame Gowda Saralamma Jeong Doo Heo Eun Hee Kim Sang Joon Lee Gon Sup Kim |
author_sort |
Sang Eun Ha |
title |
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_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_sort |
scutellarein induces fas-mediated extrinsic apoptosis and g2/m cell cycle arrest in hep3b hepatocellular carcinoma cells |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2019-01-01 |
description |
Scutellarein (SCU), a flavone found in the perennial herb <i>Scutellaria baicalensis</i>, 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. |
topic |
scutellarein flavonoid hepatocellular carcinoma apoptosis cell cycle arrest |
url |
https://www.mdpi.com/2072-6643/11/2/263 |
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