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Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells

Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal ro...

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Autores principales: Bae, Jaehoon, Lee, Kwanwoo, Park, Ji-Sun, Jung, Jinseok, Tachibana, Hirofumi, Fujimura, Yoshinori, Kumazoe, Motofumi, Lim, Jae Sung, Cho, Young-Chang, Lee, Seung-Jae, Park, Su-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777077/
https://www.ncbi.nlm.nih.gov/pubmed/36547087
http://dx.doi.org/10.3390/cimb44120426
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author Bae, Jaehoon
Lee, Kwanwoo
Park, Ji-Sun
Jung, Jinseok
Tachibana, Hirofumi
Fujimura, Yoshinori
Kumazoe, Motofumi
Lim, Jae Sung
Cho, Young-Chang
Lee, Seung-Jae
Park, Su-Jin
author_facet Bae, Jaehoon
Lee, Kwanwoo
Park, Ji-Sun
Jung, Jinseok
Tachibana, Hirofumi
Fujimura, Yoshinori
Kumazoe, Motofumi
Lim, Jae Sung
Cho, Young-Chang
Lee, Seung-Jae
Park, Su-Jin
author_sort Bae, Jaehoon
collection PubMed
description Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer.
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spelling pubmed-97770772022-12-23 Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells Bae, Jaehoon Lee, Kwanwoo Park, Ji-Sun Jung, Jinseok Tachibana, Hirofumi Fujimura, Yoshinori Kumazoe, Motofumi Lim, Jae Sung Cho, Young-Chang Lee, Seung-Jae Park, Su-Jin Curr Issues Mol Biol Article Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer. MDPI 2022-12-09 /pmc/articles/PMC9777077/ /pubmed/36547087 http://dx.doi.org/10.3390/cimb44120426 Text en © 2022 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
Bae, Jaehoon
Lee, Kwanwoo
Park, Ji-Sun
Jung, Jinseok
Tachibana, Hirofumi
Fujimura, Yoshinori
Kumazoe, Motofumi
Lim, Jae Sung
Cho, Young-Chang
Lee, Seung-Jae
Park, Su-Jin
Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells
title Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells
title_full Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells
title_fullStr Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells
title_full_unstemmed Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells
title_short Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells
title_sort phosphodiesterase 5 inhibitor potentiates epigallocatechin 3-o-gallate-induced apoptotic cell death via activation of the cgmp signaling pathway in caco-2 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777077/
https://www.ncbi.nlm.nih.gov/pubmed/36547087
http://dx.doi.org/10.3390/cimb44120426
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