Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL rece...
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Autor*in:	Manami Semba [verfasserIn] Shinji Takamatsu [verfasserIn] Sachiko Komazawa-Sakon [verfasserIn] Eiji Miyoshi [verfasserIn] Chiharu Nishiyama [verfasserIn] Hiroyasu Nakano [verfasserIn] Kenta Moriwaki [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	TRAIL apoptosis cardiac glycoside

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 13, p 6973
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:13, p 6973

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms23136973

Katalog-ID:	DOAJ024716170

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allfields	10.3390/ijms23136973 doi (DE-627)DOAJ024716170 (DE-599)DOAJdd75c487c34c45199487e93ddf3e43db DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Manami Semba verfasserin aut Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via <i<O</i<-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics. TRAIL apoptosis cardiac glycoside <i<O</i<-glycosylation Biology (General) Chemistry Shinji Takamatsu verfasserin aut Sachiko Komazawa-Sakon verfasserin aut Eiji Miyoshi verfasserin aut Chiharu Nishiyama verfasserin aut Hiroyasu Nakano verfasserin aut Kenta Moriwaki verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 13, p 6973 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:13, p 6973 https://doi.org/10.3390/ijms23136973 kostenfrei https://doaj.org/article/dd75c487c34c45199487e93ddf3e43db kostenfrei https://www.mdpi.com/1422-0067/23/13/6973 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 13, p 6973
spelling	10.3390/ijms23136973 doi (DE-627)DOAJ024716170 (DE-599)DOAJdd75c487c34c45199487e93ddf3e43db DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Manami Semba verfasserin aut Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via <i<O</i<-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics. TRAIL apoptosis cardiac glycoside <i<O</i<-glycosylation Biology (General) Chemistry Shinji Takamatsu verfasserin aut Sachiko Komazawa-Sakon verfasserin aut Eiji Miyoshi verfasserin aut Chiharu Nishiyama verfasserin aut Hiroyasu Nakano verfasserin aut Kenta Moriwaki verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 13, p 6973 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:13, p 6973 https://doi.org/10.3390/ijms23136973 kostenfrei https://doaj.org/article/dd75c487c34c45199487e93ddf3e43db kostenfrei https://www.mdpi.com/1422-0067/23/13/6973 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 13, p 6973
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callnumber-first	Q - Science
author	Manami Semba
spellingShingle	Manami Semba misc QH301-705.5 misc QD1-999 misc TRAIL misc apoptosis misc cardiac glycoside misc <i<O</i<-glycosylation misc Biology (General) misc Chemistry Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death
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topic_title	QH301-705.5 QD1-999 Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death TRAIL apoptosis cardiac glycoside <i<O</i<-glycosylation
topic	misc QH301-705.5 misc QD1-999 misc TRAIL misc apoptosis misc cardiac glycoside misc <i<O</i<-glycosylation misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc TRAIL misc apoptosis misc cardiac glycoside misc <i<O</i<-glycosylation misc Biology (General) misc Chemistry
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title_sort	proscillaridin a sensitizes human colon cancer cells to trail-induced cell death
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title_auth	Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death
abstract	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via <i<O</i<-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics.
abstractGer	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via <i<O</i<-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics.
abstract_unstemmed	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via <i<O</i<-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics.
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title_short	Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death
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Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via <i<O</i<-glycosylation. 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Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death

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