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Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand

Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we inv...

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Autores principales: Venkatarame Gowda Saralamma, Venu, Nagappan, Arulkumar, Hong, Gyeong Eun, Lee, Ho Jeong, Yumnam, Silvia, Raha, Suchismita, Heo, Jeong Doo, Lee, Sang Joon, Lee, Won Sup, Kim, Eun Hee, Kim, Gon Sup
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613330/
https://www.ncbi.nlm.nih.gov/pubmed/26393583
http://dx.doi.org/10.3390/ijms160922676
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author Venkatarame Gowda Saralamma, Venu
Nagappan, Arulkumar
Hong, Gyeong Eun
Lee, Ho Jeong
Yumnam, Silvia
Raha, Suchismita
Heo, Jeong Doo
Lee, Sang Joon
Lee, Won Sup
Kim, Eun Hee
Kim, Gon Sup
author_facet Venkatarame Gowda Saralamma, Venu
Nagappan, Arulkumar
Hong, Gyeong Eun
Lee, Ho Jeong
Yumnam, Silvia
Raha, Suchismita
Heo, Jeong Doo
Lee, Sang Joon
Lee, Won Sup
Kim, Eun Hee
Kim, Gon Sup
author_sort Venkatarame Gowda Saralamma, Venu
collection PubMed
description Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.
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spelling pubmed-46133302015-10-26 Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand Venkatarame Gowda Saralamma, Venu Nagappan, Arulkumar Hong, Gyeong Eun Lee, Ho Jeong Yumnam, Silvia Raha, Suchismita Heo, Jeong Doo Lee, Sang Joon Lee, Won Sup Kim, Eun Hee Kim, Gon Sup Int J Mol Sci Article Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer. MDPI 2015-09-18 /pmc/articles/PMC4613330/ /pubmed/26393583 http://dx.doi.org/10.3390/ijms160922676 Text en © 2015 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Venkatarame Gowda Saralamma, Venu
Nagappan, Arulkumar
Hong, Gyeong Eun
Lee, Ho Jeong
Yumnam, Silvia
Raha, Suchismita
Heo, Jeong Doo
Lee, Sang Joon
Lee, Won Sup
Kim, Eun Hee
Kim, Gon Sup
Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand
title Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand
title_full Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand
title_fullStr Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand
title_full_unstemmed Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand
title_short Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand
title_sort poncirin induces apoptosis in ags human gastric cancer cells through extrinsic apoptotic pathway by up-regulation of fas ligand
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613330/
https://www.ncbi.nlm.nih.gov/pubmed/26393583
http://dx.doi.org/10.3390/ijms160922676
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