Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells

The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-c...
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Gespeichert in:

Autor*in:	On-Yu Hong [verfasserIn] Eugene Cho [verfasserIn] Jong-Suk Kim [verfasserIn] Kwang-Hyun Park [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	mammalian target of rapamycin (mTOR) mTOR kinase inhibitor mTOR phosphorylation torin1 brazilin heme oxygenase-1

Übergeordnetes Werk:	In: Frontiers in Energy Research - Frontiers Media S.A., 2014, 10(2022)
Übergeordnetes Werk:	volume:10 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fenrg.2022.860627

Katalog-ID:	DOAJ063207222

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allfields	10.3389/fenrg.2022.860627 doi (DE-627)DOAJ063207222 (DE-599)DOAJcf9960a7bbb141a4a7a5071727ddb0da DE-627 ger DE-627 rakwb eng On-Yu Hong verfasserin aut Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells. mammalian target of rapamycin (mTOR) mTOR kinase inhibitor mTOR phosphorylation torin1 brazilin heme oxygenase-1 General Works A Eugene Cho verfasserin aut Jong-Suk Kim verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut In Frontiers in Energy Research Frontiers Media S.A., 2014 10(2022) (DE-627)768576768 (DE-600)2733788-1 2296598X nnns volume:10 year:2022 https://doi.org/10.3389/fenrg.2022.860627 kostenfrei https://doaj.org/article/cf9960a7bbb141a4a7a5071727ddb0da kostenfrei https://www.frontiersin.org/articles/10.3389/fenrg.2022.860627/full kostenfrei https://doaj.org/toc/2296-598X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
spelling	10.3389/fenrg.2022.860627 doi (DE-627)DOAJ063207222 (DE-599)DOAJcf9960a7bbb141a4a7a5071727ddb0da DE-627 ger DE-627 rakwb eng On-Yu Hong verfasserin aut Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells. mammalian target of rapamycin (mTOR) mTOR kinase inhibitor mTOR phosphorylation torin1 brazilin heme oxygenase-1 General Works A Eugene Cho verfasserin aut Jong-Suk Kim verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut In Frontiers in Energy Research Frontiers Media S.A., 2014 10(2022) (DE-627)768576768 (DE-600)2733788-1 2296598X nnns volume:10 year:2022 https://doi.org/10.3389/fenrg.2022.860627 kostenfrei https://doaj.org/article/cf9960a7bbb141a4a7a5071727ddb0da kostenfrei https://www.frontiersin.org/articles/10.3389/fenrg.2022.860627/full kostenfrei https://doaj.org/toc/2296-598X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
allfields_unstemmed	10.3389/fenrg.2022.860627 doi (DE-627)DOAJ063207222 (DE-599)DOAJcf9960a7bbb141a4a7a5071727ddb0da DE-627 ger DE-627 rakwb eng On-Yu Hong verfasserin aut Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells. mammalian target of rapamycin (mTOR) mTOR kinase inhibitor mTOR phosphorylation torin1 brazilin heme oxygenase-1 General Works A Eugene Cho verfasserin aut Jong-Suk Kim verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut In Frontiers in Energy Research Frontiers Media S.A., 2014 10(2022) (DE-627)768576768 (DE-600)2733788-1 2296598X nnns volume:10 year:2022 https://doi.org/10.3389/fenrg.2022.860627 kostenfrei https://doaj.org/article/cf9960a7bbb141a4a7a5071727ddb0da kostenfrei https://www.frontiersin.org/articles/10.3389/fenrg.2022.860627/full kostenfrei https://doaj.org/toc/2296-598X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
allfieldsGer	10.3389/fenrg.2022.860627 doi (DE-627)DOAJ063207222 (DE-599)DOAJcf9960a7bbb141a4a7a5071727ddb0da DE-627 ger DE-627 rakwb eng On-Yu Hong verfasserin aut Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells. mammalian target of rapamycin (mTOR) mTOR kinase inhibitor mTOR phosphorylation torin1 brazilin heme oxygenase-1 General Works A Eugene Cho verfasserin aut Jong-Suk Kim verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut In Frontiers in Energy Research Frontiers Media S.A., 2014 10(2022) (DE-627)768576768 (DE-600)2733788-1 2296598X nnns volume:10 year:2022 https://doi.org/10.3389/fenrg.2022.860627 kostenfrei https://doaj.org/article/cf9960a7bbb141a4a7a5071727ddb0da kostenfrei https://www.frontiersin.org/articles/10.3389/fenrg.2022.860627/full kostenfrei https://doaj.org/toc/2296-598X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
allfieldsSound	10.3389/fenrg.2022.860627 doi (DE-627)DOAJ063207222 (DE-599)DOAJcf9960a7bbb141a4a7a5071727ddb0da DE-627 ger DE-627 rakwb eng On-Yu Hong verfasserin aut Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells. mammalian target of rapamycin (mTOR) mTOR kinase inhibitor mTOR phosphorylation torin1 brazilin heme oxygenase-1 General Works A Eugene Cho verfasserin aut Jong-Suk Kim verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut Kwang-Hyun Park verfasserin aut In Frontiers in Energy Research Frontiers Media S.A., 2014 10(2022) (DE-627)768576768 (DE-600)2733788-1 2296598X nnns volume:10 year:2022 https://doi.org/10.3389/fenrg.2022.860627 kostenfrei https://doaj.org/article/cf9960a7bbb141a4a7a5071727ddb0da kostenfrei https://www.frontiersin.org/articles/10.3389/fenrg.2022.860627/full kostenfrei https://doaj.org/toc/2296-598X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
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author	On-Yu Hong
spellingShingle	On-Yu Hong misc mammalian target of rapamycin (mTOR) misc mTOR kinase inhibitor misc mTOR phosphorylation misc torin1 misc brazilin misc heme oxygenase-1 misc General Works misc A Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells
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topic_title	Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells mammalian target of rapamycin (mTOR) mTOR kinase inhibitor mTOR phosphorylation torin1 brazilin heme oxygenase-1
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title	Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells
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title_full	Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells
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title_sort	brazilin from caesalpinia sappan l. induced apoptosis via mtor and ho-1 pathway in sw480 human colon cancer cells
title_auth	Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells
abstract	The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells.
abstractGer	The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells.
abstract_unstemmed	The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells.
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title_short	Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells
url	https://doi.org/10.3389/fenrg.2022.860627 https://doaj.org/article/cf9960a7bbb141a4a7a5071727ddb0da https://www.frontiersin.org/articles/10.3389/fenrg.2022.860627/full https://doaj.org/toc/2296-598X
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up_date	2024-07-03T16:26:16.177Z
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Brazilin From Caesalpinia sappan L. Induced Apoptosis via mTOR and HO-1 Pathway in SW480 Human Colon Cancer Cells

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