Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth
Octyl gallate (OG) is a common antioxidant and preservative safely used in food additive and cosmetics. In this study, OG exhibited an activity to induce apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells. It induced BNIP3L level and facilitated physical associations of BNIP3L with Bcl-2 as...
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MDPI AG
2019-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/1/91 |
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| author | Kee Voon Chua Chi-Shuan Fan Chia-Chi Chen Li-Li Chen Shu-Chen Hsieh Tze-Sing Huang |
| author_facet | Kee Voon Chua Chi-Shuan Fan Chia-Chi Chen Li-Li Chen Shu-Chen Hsieh Tze-Sing Huang |
| author_sort | Kee Voon Chua |
| collection | DOAJ |
| description | Octyl gallate (OG) is a common antioxidant and preservative safely used in food additive and cosmetics. In this study, OG exhibited an activity to induce apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells. It induced BNIP3L level and facilitated physical associations of BNIP3L with Bcl-2 as well as Bcl-X<sub>L</sub> to set the mitochondrial Bax/Bak channels free for cytochrome <i>c</i> release. In addition, in vivo evaluation also showed that daily oral administration of OG was efficacious to prevent the tumor growth of PDAC cell grafts. Considering PDAC is a desmoplastic tumor consisting of many cancer-associated fibroblasts (CAFs), we further evaluated the efficacy of OG in a CAFs-involved PDAC mouse model. Endothelial-to-mesenchymal transition (EndoMT) is an important source of CAFs. The mix of EndoMT-derived CAFs with PDAC cell grafts significantly recruited myeloid-derived macrophages but prevented immune T cells. HSP90α secreted by EndoMT-derived CAFs further induced macrophage M2-polarization and more HSP90α secretion to expedite PDAC tumor growth. OG exhibited its potent efficacy against the tumor growth, M2-macrophages, and serum HSP90α level in the EndoMT-involved PDAC mouse model. CD91 and TLR4 are cell-surface receptors for extracellular HSP90α (eHSP90α). OG blocked eHSP90α−TLR4 ligation and, thus, prevented eHSP90α-induced M2-macrophages and more HSP90α secretion from macrophages and PDAC cells. |
| first_indexed | 2024-03-12T19:57:51Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:57:51Z |
| publishDate | 2019-12-01 |
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| spelling | doaj.art-5070de37a2a14fc4883dc93a36385fce2023-08-02T02:41:41ZengMDPI AGCells2073-44092019-12-01919110.3390/cells9010091cells9010091Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor GrowthKee Voon Chua0Chi-Shuan Fan1Chia-Chi Chen2Li-Li Chen3Shu-Chen Hsieh4Tze-Sing Huang5National Institute of Cancer Research, National Health Research Institutes, Miaoli 350, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Miaoli 350, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Miaoli 350, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Miaoli 350, TaiwanGraduate Institute of Food Science and Technology, College of Bioresources and Agriculture, National Taiwan University, Taipei 106, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Miaoli 350, TaiwanOctyl gallate (OG) is a common antioxidant and preservative safely used in food additive and cosmetics. In this study, OG exhibited an activity to induce apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells. It induced BNIP3L level and facilitated physical associations of BNIP3L with Bcl-2 as well as Bcl-X<sub>L</sub> to set the mitochondrial Bax/Bak channels free for cytochrome <i>c</i> release. In addition, in vivo evaluation also showed that daily oral administration of OG was efficacious to prevent the tumor growth of PDAC cell grafts. Considering PDAC is a desmoplastic tumor consisting of many cancer-associated fibroblasts (CAFs), we further evaluated the efficacy of OG in a CAFs-involved PDAC mouse model. Endothelial-to-mesenchymal transition (EndoMT) is an important source of CAFs. The mix of EndoMT-derived CAFs with PDAC cell grafts significantly recruited myeloid-derived macrophages but prevented immune T cells. HSP90α secreted by EndoMT-derived CAFs further induced macrophage M2-polarization and more HSP90α secretion to expedite PDAC tumor growth. OG exhibited its potent efficacy against the tumor growth, M2-macrophages, and serum HSP90α level in the EndoMT-involved PDAC mouse model. CD91 and TLR4 are cell-surface receptors for extracellular HSP90α (eHSP90α). OG blocked eHSP90α−TLR4 ligation and, thus, prevented eHSP90α-induced M2-macrophages and more HSP90α secretion from macrophages and PDAC cells.https://www.mdpi.com/2073-4409/9/1/91octyl gallateendothelial-to-mesenchymal transitioncancer-associated fibroblastsmyeloid-derived macrophagesextracellular hsp90α |
| spellingShingle | Kee Voon Chua Chi-Shuan Fan Chia-Chi Chen Li-Li Chen Shu-Chen Hsieh Tze-Sing Huang Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth Cells octyl gallate endothelial-to-mesenchymal transition cancer-associated fibroblasts myeloid-derived macrophages extracellular hsp90α |
| title | Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth |
| title_full | Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth |
| title_fullStr | Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth |
| title_full_unstemmed | Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth |
| title_short | Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth |
| title_sort | octyl gallate induces pancreatic ductal adenocarcinoma cell apoptosis and suppresses endothelial mesenchymal transition promoted m2 macrophages hsp90α secretion and tumor growth |
| topic | octyl gallate endothelial-to-mesenchymal transition cancer-associated fibroblasts myeloid-derived macrophages extracellular hsp90α |
| url | https://www.mdpi.com/2073-4409/9/1/91 |
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