Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells

Abstract Breast cancer is the leading cause of cancer-related death for women. In breast cancer treatment, targeted therapy would be more effective and less harmful than radiotherapy or systemic chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce ap...

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Autores principales: Ya-Han Liang, Jiann-Ming Wu, Jui-Wen Teng, Eric Hung, Hwai-Shi Wang
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/fcf0f9776e4642c9966cb1624ccaf2f3
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spelling oai:doaj.org-article:fcf0f9776e4642c9966cb1624ccaf2f32021-12-02T17:55:13ZEmbelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells10.1038/s41598-021-94006-w2045-2322https://doaj.org/article/fcf0f9776e4642c9966cb1624ccaf2f32021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94006-whttps://doaj.org/toc/2045-2322Abstract Breast cancer is the leading cause of cancer-related death for women. In breast cancer treatment, targeted therapy would be more effective and less harmful than radiotherapy or systemic chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in cancer cells but not in normal cells. Mesenchymal stem cells have shown great therapeutic potential in cancer therapy owing to their ability of homing to tumor sites and secreting many kinds of anti-tumor proteins including TRAIL. In this study, we found that IL-1β-stimulated human umbilical cord-derived mesenchymal stem cells (hUCMSCs) enhance the expression of membrane-bound and soluble TRAIL. Cellular FADD-like IL-1β-converting enzyme inhibitory protein (cFLIP) is an important regulator in TRAIL-mediated apoptosis and relates to TRAIL resistance in cancer cells. Previous studies have shown that embelin, which is extracted from Embelia ribes, can increase the TRAIL sensitivity of cancer cells by reducing cFLIP expression. Here we have demonstrated that cFLIPL is correlated with TRAIL-resistance and that embelin effectively downregulates cFLIPL in breast cancer cells. Moreover, co-culture of IL-1β-stimulated hUCMSCs with embelin-treated breast cancer cells could effectively induce apoptosis in breast cancer cells. The combined effects of embelin and IL-1β-stimulated hUCMSCs may provide a new therapeutic strategy for breast cancer therapy.Ya-Han LiangJiann-Ming WuJui-Wen TengEric HungHwai-Shi WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ya-Han Liang
Jiann-Ming Wu
Jui-Wen Teng
Eric Hung
Hwai-Shi Wang
Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells
description Abstract Breast cancer is the leading cause of cancer-related death for women. In breast cancer treatment, targeted therapy would be more effective and less harmful than radiotherapy or systemic chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in cancer cells but not in normal cells. Mesenchymal stem cells have shown great therapeutic potential in cancer therapy owing to their ability of homing to tumor sites and secreting many kinds of anti-tumor proteins including TRAIL. In this study, we found that IL-1β-stimulated human umbilical cord-derived mesenchymal stem cells (hUCMSCs) enhance the expression of membrane-bound and soluble TRAIL. Cellular FADD-like IL-1β-converting enzyme inhibitory protein (cFLIP) is an important regulator in TRAIL-mediated apoptosis and relates to TRAIL resistance in cancer cells. Previous studies have shown that embelin, which is extracted from Embelia ribes, can increase the TRAIL sensitivity of cancer cells by reducing cFLIP expression. Here we have demonstrated that cFLIPL is correlated with TRAIL-resistance and that embelin effectively downregulates cFLIPL in breast cancer cells. Moreover, co-culture of IL-1β-stimulated hUCMSCs with embelin-treated breast cancer cells could effectively induce apoptosis in breast cancer cells. The combined effects of embelin and IL-1β-stimulated hUCMSCs may provide a new therapeutic strategy for breast cancer therapy.
format article
author Ya-Han Liang
Jiann-Ming Wu
Jui-Wen Teng
Eric Hung
Hwai-Shi Wang
author_facet Ya-Han Liang
Jiann-Ming Wu
Jui-Wen Teng
Eric Hung
Hwai-Shi Wang
author_sort Ya-Han Liang
title Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells
title_short Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells
title_full Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells
title_fullStr Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells
title_full_unstemmed Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells
title_sort embelin downregulated cflip in breast cancer cell lines facilitate anti-tumor effect of il-1β-stimulated human umbilical cord mesenchymal stem cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/fcf0f9776e4642c9966cb1624ccaf2f3
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AT erichung embelindownregulatedcflipinbreastcancercelllinesfacilitateantitumoreffectofil1bstimulatedhumanumbilicalcordmesenchymalstemcells
AT hwaishiwang embelindownregulatedcflipinbreastcancercelllinesfacilitateantitumoreffectofil1bstimulatedhumanumbilicalcordmesenchymalstemcells
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