A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis

Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a...
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Autor*in:	Ma, Liang [verfasserIn] Xuan, Xiaojing Fan, Minghui Zhang, Yumeng Yuan, Guozan Huang, Guozheng Liu, Zi

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Paraptosis Apoptosis 8-Hydroxyquinoline derivative ER stress ERK Breast cancer

Anmerkung:	© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022

Übergeordnetes Werk:	Enthalten in: Apoptosis - Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996, 27(2022), 7-8 vom: 08. Juni, Seite 577-589
Übergeordnetes Werk:	volume:27 ; year:2022 ; number:7-8 ; day:08 ; month:06 ; pages:577-589

Links:	Volltext

DOI / URN:	10.1007/s10495-022-01737-w

Katalog-ID:	SPR047665351

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100	1		\|a Ma, Liang \|e verfasserin \|0 (orcid)0000-0001-9131-4512 \|4 aut
245	1	2	\|a A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis
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520			\|a Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy.
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700	1		\|a Xuan, Xiaojing \|4 aut
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700	1		\|a Zhang, Yumeng \|4 aut
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700	1		\|a Huang, Guozheng \|4 aut
700	1		\|a Liu, Zi \|0 (orcid)0000-0002-1353-4461 \|4 aut
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912			\|a GBV_ILN_110
912			\|a GBV_ILN_120
912			\|a GBV_ILN_138
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_152
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_171
912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_250
912			\|a GBV_ILN_281
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
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912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2037
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2039
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
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912			\|a GBV_ILN_2057
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2065
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2088
912			\|a GBV_ILN_2093
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2107
912			\|a GBV_ILN_2108
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
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Indexfelder

author_variant	l m lm x x xx m f mf y z yz g y gy g h gh z l zl
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publishDate	2022
allfields	10.1007/s10495-022-01737-w doi (DE-627)SPR047665351 (SPR)s10495-022-01737-w-e DE-627 ger DE-627 rakwb eng Ma, Liang verfasserin (orcid)0000-0001-9131-4512 aut A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. Paraptosis (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 8-Hydroxyquinoline derivative (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 ERK (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Xuan, Xiaojing aut Fan, Minghui aut Zhang, Yumeng aut Yuan, Guozan aut Huang, Guozheng aut Liu, Zi (orcid)0000-0002-1353-4461 aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 27(2022), 7-8 vom: 08. Juni, Seite 577-589 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:27 year:2022 number:7-8 day:08 month:06 pages:577-589 https://dx.doi.org/10.1007/s10495-022-01737-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2022 7-8 08 06 577-589
spelling	10.1007/s10495-022-01737-w doi (DE-627)SPR047665351 (SPR)s10495-022-01737-w-e DE-627 ger DE-627 rakwb eng Ma, Liang verfasserin (orcid)0000-0001-9131-4512 aut A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. Paraptosis (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 8-Hydroxyquinoline derivative (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 ERK (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Xuan, Xiaojing aut Fan, Minghui aut Zhang, Yumeng aut Yuan, Guozan aut Huang, Guozheng aut Liu, Zi (orcid)0000-0002-1353-4461 aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 27(2022), 7-8 vom: 08. Juni, Seite 577-589 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:27 year:2022 number:7-8 day:08 month:06 pages:577-589 https://dx.doi.org/10.1007/s10495-022-01737-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2022 7-8 08 06 577-589
allfields_unstemmed	10.1007/s10495-022-01737-w doi (DE-627)SPR047665351 (SPR)s10495-022-01737-w-e DE-627 ger DE-627 rakwb eng Ma, Liang verfasserin (orcid)0000-0001-9131-4512 aut A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. Paraptosis (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 8-Hydroxyquinoline derivative (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 ERK (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Xuan, Xiaojing aut Fan, Minghui aut Zhang, Yumeng aut Yuan, Guozan aut Huang, Guozheng aut Liu, Zi (orcid)0000-0002-1353-4461 aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 27(2022), 7-8 vom: 08. Juni, Seite 577-589 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:27 year:2022 number:7-8 day:08 month:06 pages:577-589 https://dx.doi.org/10.1007/s10495-022-01737-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2022 7-8 08 06 577-589
allfieldsGer	10.1007/s10495-022-01737-w doi (DE-627)SPR047665351 (SPR)s10495-022-01737-w-e DE-627 ger DE-627 rakwb eng Ma, Liang verfasserin (orcid)0000-0001-9131-4512 aut A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. Paraptosis (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 8-Hydroxyquinoline derivative (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 ERK (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Xuan, Xiaojing aut Fan, Minghui aut Zhang, Yumeng aut Yuan, Guozan aut Huang, Guozheng aut Liu, Zi (orcid)0000-0002-1353-4461 aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 27(2022), 7-8 vom: 08. Juni, Seite 577-589 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:27 year:2022 number:7-8 day:08 month:06 pages:577-589 https://dx.doi.org/10.1007/s10495-022-01737-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2022 7-8 08 06 577-589
allfieldsSound	10.1007/s10495-022-01737-w doi (DE-627)SPR047665351 (SPR)s10495-022-01737-w-e DE-627 ger DE-627 rakwb eng Ma, Liang verfasserin (orcid)0000-0001-9131-4512 aut A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. Paraptosis (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 8-Hydroxyquinoline derivative (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 ERK (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Xuan, Xiaojing aut Fan, Minghui aut Zhang, Yumeng aut Yuan, Guozan aut Huang, Guozheng aut Liu, Zi (orcid)0000-0002-1353-4461 aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 27(2022), 7-8 vom: 08. Juni, Seite 577-589 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:27 year:2022 number:7-8 day:08 month:06 pages:577-589 https://dx.doi.org/10.1007/s10495-022-01737-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2022 7-8 08 06 577-589
language	English
source	Enthalten in Apoptosis 27(2022), 7-8 vom: 08. Juni, Seite 577-589 volume:27 year:2022 number:7-8 day:08 month:06 pages:577-589
sourceStr	Enthalten in Apoptosis 27(2022), 7-8 vom: 08. Juni, Seite 577-589 volume:27 year:2022 number:7-8 day:08 month:06 pages:577-589
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Paraptosis Apoptosis 8-Hydroxyquinoline derivative ER stress ERK Breast cancer
isfreeaccess_bool	false
container_title	Apoptosis
authorswithroles_txt_mv	Ma, Liang @@aut@@ Xuan, Xiaojing @@aut@@ Fan, Minghui @@aut@@ Zhang, Yumeng @@aut@@ Yuan, Guozan @@aut@@ Huang, Guozheng @@aut@@ Liu, Zi @@aut@@
publishDateDaySort_date	2022-06-08T00:00:00Z
hierarchy_top_id	306311577
id	SPR047665351
language_de	englisch
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author	Ma, Liang
spellingShingle	Ma, Liang misc Paraptosis misc Apoptosis misc 8-Hydroxyquinoline derivative misc ER stress misc ERK misc Breast cancer A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis
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topic_title	A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis Paraptosis (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 8-Hydroxyquinoline derivative (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 ERK (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213
topic	misc Paraptosis misc Apoptosis misc 8-Hydroxyquinoline derivative misc ER stress misc ERK misc Breast cancer
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title	A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis
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title_full	A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis
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author_browse	Ma, Liang Xuan, Xiaojing Fan, Minghui Zhang, Yumeng Yuan, Guozan Huang, Guozheng Liu, Zi
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title_sort	novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis
title_auth	A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis
abstract	Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022
abstractGer	Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022
abstract_unstemmed	Abstract Chemotherapy represents one of the main conventional therapies for breast cancer. However, tumor cells develop mechanisms to evade chemotherapeutic-induced apoptosis. Thus, it is of great significance to induce non-apoptotic cell death modes, such as paraptosis, in breast cancer. Herein, a novel 8-hydroxyquinoline derivative, 5,7-dibromo-8-(methoxymethoxy)-2-methylquinoline (HQ-11), was obtained and its potential anti-breast cancer mechanisms were investigated. Our results showed that extensive cytoplasmic vacuoles derived from the endoplasmic reticulum (ER) and mitochondria were appeared in MCF7 and MDA-MB-231 breast cancer cells by HQ-11 incubation, and pretreatment of cycloheximide was able to inhibit this vacuolation and HQ-11-induced cell death, showing the characteristics of paraptosis. ER stress was involved in HQ-11-caused paraptosis evidenced by the increase of glucose-regulated protein 78, C/EBP homologous protein and polyubiquitinated proteins. Molecular docking analysis revealed a favorable binding mode of HQ-11 in the active site of the chymotrypsin-like β5 subunit of the proteasome, indicative of proteasome dysfunction under HQ-11 treatment, which might result in further aggravated ER stress. Furthermore, treatment of HQ-11 resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun $ NH_{2} $-terminal kinase, and inhibition of ERK with U0126 significantly attenuated HQ-11-induced ER stress and paraptosis. In addition, exposure to HQ-11 also caused apoptosis in breast cancer cells partially through activation of ERK pathway. All these results conclusively indicate that HQ-11 triggers two distinct cell death modes via inhibition of proteasome and activation of ERK pathway in breast cancer cells, providing a promising candidate in future anti-breast cancer therapy. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022
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container_issue	7-8
title_short	A novel 8-hydroxyquinoline derivative induces breast cancer cell death through paraptosis and apoptosis
url	https://dx.doi.org/10.1007/s10495-022-01737-w
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author2	Xuan, Xiaojing Fan, Minghui Zhang, Yumeng Yuan, Guozan Huang, Guozheng Liu, Zi
author2Str	Xuan, Xiaojing Fan, Minghui Zhang, Yumeng Yuan, Guozan Huang, Guozheng Liu, Zi
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doi_str	10.1007/s10495-022-01737-w
up_date	2024-07-03T14:12:15.214Z
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