A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation

We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 val...
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Autor*in:	Umasankar De [verfasserIn] Ji Yeon Son [verfasserIn] Richa Sachan [verfasserIn] Yu Jin Park [verfasserIn] Dongwan Kang [verfasserIn] Kyungsil Yoon [verfasserIn] Byung Mu Lee [verfasserIn] In Su Kim [verfasserIn] Hyung Ryong Moon [verfasserIn] Hyung Sik Kim [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 19(2018), 9, p 2743
Übergeordnetes Werk:	volume:19 ; year:2018 ; number:9, p 2743

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/ijms19092743

Katalog-ID:	DOAJ052519716

Internformat


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Indexfelder

author_variant	u d ud j y s jys r s rs y j p yjp d k dk k y ky b m l bml i s k isk h r m hrm h s k hsk
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allfields	10.3390/ijms19092743 doi (DE-627)DOAJ052519716 (DE-599)DOAJ8658bbf420c147fa88e8fab1f493718f DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Umasankar De verfasserin aut A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers. histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer Biology (General) Chemistry Ji Yeon Son verfasserin aut Richa Sachan verfasserin aut Yu Jin Park verfasserin aut Dongwan Kang verfasserin aut Kyungsil Yoon verfasserin aut Byung Mu Lee verfasserin aut In Su Kim verfasserin aut Hyung Ryong Moon verfasserin aut Hyung Sik Kim verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 19(2018), 9, p 2743 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:19 year:2018 number:9, p 2743 https://doi.org/10.3390/ijms19092743 kostenfrei https://doaj.org/article/8658bbf420c147fa88e8fab1f493718f kostenfrei http://www.mdpi.com/1422-0067/19/9/2743 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 19 2018 9, p 2743
spelling	10.3390/ijms19092743 doi (DE-627)DOAJ052519716 (DE-599)DOAJ8658bbf420c147fa88e8fab1f493718f DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Umasankar De verfasserin aut A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers. histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer Biology (General) Chemistry Ji Yeon Son verfasserin aut Richa Sachan verfasserin aut Yu Jin Park verfasserin aut Dongwan Kang verfasserin aut Kyungsil Yoon verfasserin aut Byung Mu Lee verfasserin aut In Su Kim verfasserin aut Hyung Ryong Moon verfasserin aut Hyung Sik Kim verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 19(2018), 9, p 2743 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:19 year:2018 number:9, p 2743 https://doi.org/10.3390/ijms19092743 kostenfrei https://doaj.org/article/8658bbf420c147fa88e8fab1f493718f kostenfrei http://www.mdpi.com/1422-0067/19/9/2743 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 19 2018 9, p 2743
allfields_unstemmed	10.3390/ijms19092743 doi (DE-627)DOAJ052519716 (DE-599)DOAJ8658bbf420c147fa88e8fab1f493718f DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Umasankar De verfasserin aut A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers. histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer Biology (General) Chemistry Ji Yeon Son verfasserin aut Richa Sachan verfasserin aut Yu Jin Park verfasserin aut Dongwan Kang verfasserin aut Kyungsil Yoon verfasserin aut Byung Mu Lee verfasserin aut In Su Kim verfasserin aut Hyung Ryong Moon verfasserin aut Hyung Sik Kim verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 19(2018), 9, p 2743 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:19 year:2018 number:9, p 2743 https://doi.org/10.3390/ijms19092743 kostenfrei https://doaj.org/article/8658bbf420c147fa88e8fab1f493718f kostenfrei http://www.mdpi.com/1422-0067/19/9/2743 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 19 2018 9, p 2743
allfieldsGer	10.3390/ijms19092743 doi (DE-627)DOAJ052519716 (DE-599)DOAJ8658bbf420c147fa88e8fab1f493718f DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Umasankar De verfasserin aut A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers. histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer Biology (General) Chemistry Ji Yeon Son verfasserin aut Richa Sachan verfasserin aut Yu Jin Park verfasserin aut Dongwan Kang verfasserin aut Kyungsil Yoon verfasserin aut Byung Mu Lee verfasserin aut In Su Kim verfasserin aut Hyung Ryong Moon verfasserin aut Hyung Sik Kim verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 19(2018), 9, p 2743 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:19 year:2018 number:9, p 2743 https://doi.org/10.3390/ijms19092743 kostenfrei https://doaj.org/article/8658bbf420c147fa88e8fab1f493718f kostenfrei http://www.mdpi.com/1422-0067/19/9/2743 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 19 2018 9, p 2743
allfieldsSound	10.3390/ijms19092743 doi (DE-627)DOAJ052519716 (DE-599)DOAJ8658bbf420c147fa88e8fab1f493718f DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Umasankar De verfasserin aut A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers. histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer Biology (General) Chemistry Ji Yeon Son verfasserin aut Richa Sachan verfasserin aut Yu Jin Park verfasserin aut Dongwan Kang verfasserin aut Kyungsil Yoon verfasserin aut Byung Mu Lee verfasserin aut In Su Kim verfasserin aut Hyung Ryong Moon verfasserin aut Hyung Sik Kim verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 19(2018), 9, p 2743 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:19 year:2018 number:9, p 2743 https://doi.org/10.3390/ijms19092743 kostenfrei https://doaj.org/article/8658bbf420c147fa88e8fab1f493718f kostenfrei http://www.mdpi.com/1422-0067/19/9/2743 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 19 2018 9, p 2743
language	English
source	In International Journal of Molecular Sciences 19(2018), 9, p 2743 volume:19 year:2018 number:9, p 2743
sourceStr	In International Journal of Molecular Sciences 19(2018), 9, p 2743 volume:19 year:2018 number:9, p 2743
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Umasankar De @@aut@@ Ji Yeon Son @@aut@@ Richa Sachan @@aut@@ Yu Jin Park @@aut@@ Dongwan Kang @@aut@@ Kyungsil Yoon @@aut@@ Byung Mu Lee @@aut@@ In Su Kim @@aut@@ Hyung Ryong Moon @@aut@@ Hyung Sik Kim @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ052519716
language_de	englisch
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callnumber-first	Q - Science
author	Umasankar De
spellingShingle	Umasankar De misc QH301-705.5 misc QD1-999 misc histone deacetylase inhibitor misc MHY2256 misc p53 misc apoptosis misc autophagy misc Ishikawa misc endometrial cancer misc Biology (General) misc Chemistry A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation
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topic_title	QH301-705.5 QD1-999 A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation histone deacetylase inhibitor MHY2256 p53 apoptosis autophagy Ishikawa endometrial cancer
topic	misc QH301-705.5 misc QD1-999 misc histone deacetylase inhibitor misc MHY2256 misc p53 misc apoptosis misc autophagy misc Ishikawa misc endometrial cancer misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc histone deacetylase inhibitor misc MHY2256 misc p53 misc apoptosis misc autophagy misc Ishikawa misc endometrial cancer misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc histone deacetylase inhibitor misc MHY2256 misc p53 misc apoptosis misc autophagy misc Ishikawa misc endometrial cancer misc Biology (General) misc Chemistry
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title	A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation
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title_full	A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation
author_sort	Umasankar De
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author_browse	Umasankar De Ji Yeon Son Richa Sachan Yu Jin Park Dongwan Kang Kyungsil Yoon Byung Mu Lee In Su Kim Hyung Ryong Moon Hyung Sik Kim
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author-letter	Umasankar De
doi_str_mv	10.3390/ijms19092743
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title_sort	new synthetic histone deacetylase inhibitor, mhy2256, induces apoptosis and autophagy cell death in endometrial cancer cells via p53 acetylation
callnumber	QH301-705.5
title_auth	A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation
abstract	We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.
abstractGer	We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.
abstract_unstemmed	We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.
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container_issue	9, p 2743
title_short	A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation
url	https://doi.org/10.3390/ijms19092743 https://doaj.org/article/8658bbf420c147fa88e8fab1f493718f http://www.mdpi.com/1422-0067/19/9/2743 https://doaj.org/toc/1422-0067
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up_date	2024-07-04T01:22:22.763Z
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