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Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells

Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepa...

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Autores principales: Bhosale, Pritam Bhagwan, Kim, Hun Hwan, Abusaliya, Abuyaseer, Jeong, Se Hyo, Park, Min Yeong, Kim, Hyun-Wook, Seong, Je Kyung, Ahn, Meejung, Park, Kwang Il, Heo, Jeong Doo, Kim, Young Sil, Kim, Gon Sup
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377660/
https://www.ncbi.nlm.nih.gov/pubmed/37509167
http://dx.doi.org/10.3390/biom13071131
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author Bhosale, Pritam Bhagwan
Kim, Hun Hwan
Abusaliya, Abuyaseer
Jeong, Se Hyo
Park, Min Yeong
Kim, Hyun-Wook
Seong, Je Kyung
Ahn, Meejung
Park, Kwang Il
Heo, Jeong Doo
Kim, Young Sil
Kim, Gon Sup
author_facet Bhosale, Pritam Bhagwan
Kim, Hun Hwan
Abusaliya, Abuyaseer
Jeong, Se Hyo
Park, Min Yeong
Kim, Hyun-Wook
Seong, Je Kyung
Ahn, Meejung
Park, Kwang Il
Heo, Jeong Doo
Kim, Young Sil
Kim, Gon Sup
author_sort Bhosale, Pritam Bhagwan
collection PubMed
description Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepatocellular cancer (HCC) is a major health concern because of its adverse prognosis and side effects of chemotherapeutic agents. In the present study, we determine the impact of apigetrin on HepG2 cells and its cell death mechanism. Apigetrin reduced HepG2 cell proliferation with morphological changes and floating cells in treated cells. Colony formation and wound healing assays showed a reduced cell number in treatment groups. Further, we checked for the cell cycle through flow cytometry to understand the cell death mechanism. Apigetrin induced G2/M phase arrest in HepG2 cells by regulating Cyclin B1 and CDK1 protein levels in HepG2 cells. Annexin V and propidium iodide (PI) staining was performed to confirm the apoptotic cell population in treated groups. At the higher concentration, apigetrin showed a late apoptotic population in HepG2 cells. Chromatin condensation was also found in the treatment groups. Western blot analysis showed an increased expression of extrinsic apoptotic proteins such as FasL, Cleaved caspase 8, Cleaved caspase 3, and cleavage of PARP. In comparison, intrinsic apoptotic pathway markers showed no changes in Bax, Bcl-xL, and Cleaved caspase 9. Altogether, these findings strongly indicate that apigetrin causes cell death in HepG2 cells through the extrinsic apoptotic pathway, and that the intrinsic/mitochondrial pathway is not involved.
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spelling pubmed-103776602023-07-29 Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells Bhosale, Pritam Bhagwan Kim, Hun Hwan Abusaliya, Abuyaseer Jeong, Se Hyo Park, Min Yeong Kim, Hyun-Wook Seong, Je Kyung Ahn, Meejung Park, Kwang Il Heo, Jeong Doo Kim, Young Sil Kim, Gon Sup Biomolecules Article Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepatocellular cancer (HCC) is a major health concern because of its adverse prognosis and side effects of chemotherapeutic agents. In the present study, we determine the impact of apigetrin on HepG2 cells and its cell death mechanism. Apigetrin reduced HepG2 cell proliferation with morphological changes and floating cells in treated cells. Colony formation and wound healing assays showed a reduced cell number in treatment groups. Further, we checked for the cell cycle through flow cytometry to understand the cell death mechanism. Apigetrin induced G2/M phase arrest in HepG2 cells by regulating Cyclin B1 and CDK1 protein levels in HepG2 cells. Annexin V and propidium iodide (PI) staining was performed to confirm the apoptotic cell population in treated groups. At the higher concentration, apigetrin showed a late apoptotic population in HepG2 cells. Chromatin condensation was also found in the treatment groups. Western blot analysis showed an increased expression of extrinsic apoptotic proteins such as FasL, Cleaved caspase 8, Cleaved caspase 3, and cleavage of PARP. In comparison, intrinsic apoptotic pathway markers showed no changes in Bax, Bcl-xL, and Cleaved caspase 9. Altogether, these findings strongly indicate that apigetrin causes cell death in HepG2 cells through the extrinsic apoptotic pathway, and that the intrinsic/mitochondrial pathway is not involved. MDPI 2023-07-14 /pmc/articles/PMC10377660/ /pubmed/37509167 http://dx.doi.org/10.3390/biom13071131 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bhosale, Pritam Bhagwan
Kim, Hun Hwan
Abusaliya, Abuyaseer
Jeong, Se Hyo
Park, Min Yeong
Kim, Hyun-Wook
Seong, Je Kyung
Ahn, Meejung
Park, Kwang Il
Heo, Jeong Doo
Kim, Young Sil
Kim, Gon Sup
Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells
title Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells
title_full Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells
title_fullStr Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells
title_full_unstemmed Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells
title_short Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells
title_sort inhibition of cell proliferation and cell death by apigetrin through death receptor-mediated pathway in hepatocellular cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377660/
https://www.ncbi.nlm.nih.gov/pubmed/37509167
http://dx.doi.org/10.3390/biom13071131
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