MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer

Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY...
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Autor*in:	Jae Heun Chung [verfasserIn] Ho Jung Choi [verfasserIn] Yong Jung Kang [verfasserIn] Yun Seong Kim [verfasserIn] Sang-Yull Lee [verfasserIn] Ryuk Jun Kwon [verfasserIn] Han-Sol Jeong [verfasserIn] Su-Jung Park [verfasserIn] Yeongmu Jeong [verfasserIn] Dongwan Kang [verfasserIn] Jeongin Ko [verfasserIn] SangGyun Noh [verfasserIn] Hae Young Chung [verfasserIn] Hyung Ryong Moon [verfasserIn] Seong Hoon Yoon [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein

Übergeordnetes Werk:	In: Experimental Hematology & Oncology - BMC, 2012, 11(2022), 1, Seite 12
Übergeordnetes Werk:	volume:11 ; year:2022 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s40164-022-00324-8

Katalog-ID:	DOAJ08445279X

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520			\|a Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.
650		4	\|a Lung cancer
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650		4	\|a cAMP response element-binding protein
653		0	\|a Diseases of the blood and blood-forming organs
653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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allfields	10.1186/s40164-022-00324-8 doi (DE-627)DOAJ08445279X (DE-599)DOAJa199f05f9eec470bbb79bf94c554eaad DE-627 ger DE-627 rakwb eng RC633-647.5 RC254-282 Jae Heun Chung verfasserin aut MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment. Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein Diseases of the blood and blood-forming organs Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ho Jung Choi verfasserin aut Yong Jung Kang verfasserin aut Yun Seong Kim verfasserin aut Sang-Yull Lee verfasserin aut Ryuk Jun Kwon verfasserin aut Han-Sol Jeong verfasserin aut Su-Jung Park verfasserin aut Yeongmu Jeong verfasserin aut Dongwan Kang verfasserin aut Jeongin Ko verfasserin aut SangGyun Noh verfasserin aut Hae Young Chung verfasserin aut Hyung Ryong Moon verfasserin aut Seong Hoon Yoon verfasserin aut In Experimental Hematology & Oncology BMC, 2012 11(2022), 1, Seite 12 (DE-627)718833341 (DE-600)2669066-4 21623619 nnns volume:11 year:2022 number:1 pages:12 https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/article/a199f05f9eec470bbb79bf94c554eaad kostenfrei https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/toc/2162-3619 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 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 11 2022 1 12
spelling	10.1186/s40164-022-00324-8 doi (DE-627)DOAJ08445279X (DE-599)DOAJa199f05f9eec470bbb79bf94c554eaad DE-627 ger DE-627 rakwb eng RC633-647.5 RC254-282 Jae Heun Chung verfasserin aut MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment. Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein Diseases of the blood and blood-forming organs Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ho Jung Choi verfasserin aut Yong Jung Kang verfasserin aut Yun Seong Kim verfasserin aut Sang-Yull Lee verfasserin aut Ryuk Jun Kwon verfasserin aut Han-Sol Jeong verfasserin aut Su-Jung Park verfasserin aut Yeongmu Jeong verfasserin aut Dongwan Kang verfasserin aut Jeongin Ko verfasserin aut SangGyun Noh verfasserin aut Hae Young Chung verfasserin aut Hyung Ryong Moon verfasserin aut Seong Hoon Yoon verfasserin aut In Experimental Hematology & Oncology BMC, 2012 11(2022), 1, Seite 12 (DE-627)718833341 (DE-600)2669066-4 21623619 nnns volume:11 year:2022 number:1 pages:12 https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/article/a199f05f9eec470bbb79bf94c554eaad kostenfrei https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/toc/2162-3619 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 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 11 2022 1 12
allfields_unstemmed	10.1186/s40164-022-00324-8 doi (DE-627)DOAJ08445279X (DE-599)DOAJa199f05f9eec470bbb79bf94c554eaad DE-627 ger DE-627 rakwb eng RC633-647.5 RC254-282 Jae Heun Chung verfasserin aut MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment. Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein Diseases of the blood and blood-forming organs Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ho Jung Choi verfasserin aut Yong Jung Kang verfasserin aut Yun Seong Kim verfasserin aut Sang-Yull Lee verfasserin aut Ryuk Jun Kwon verfasserin aut Han-Sol Jeong verfasserin aut Su-Jung Park verfasserin aut Yeongmu Jeong verfasserin aut Dongwan Kang verfasserin aut Jeongin Ko verfasserin aut SangGyun Noh verfasserin aut Hae Young Chung verfasserin aut Hyung Ryong Moon verfasserin aut Seong Hoon Yoon verfasserin aut In Experimental Hematology & Oncology BMC, 2012 11(2022), 1, Seite 12 (DE-627)718833341 (DE-600)2669066-4 21623619 nnns volume:11 year:2022 number:1 pages:12 https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/article/a199f05f9eec470bbb79bf94c554eaad kostenfrei https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/toc/2162-3619 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 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 11 2022 1 12
allfieldsGer	10.1186/s40164-022-00324-8 doi (DE-627)DOAJ08445279X (DE-599)DOAJa199f05f9eec470bbb79bf94c554eaad DE-627 ger DE-627 rakwb eng RC633-647.5 RC254-282 Jae Heun Chung verfasserin aut MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment. Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein Diseases of the blood and blood-forming organs Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ho Jung Choi verfasserin aut Yong Jung Kang verfasserin aut Yun Seong Kim verfasserin aut Sang-Yull Lee verfasserin aut Ryuk Jun Kwon verfasserin aut Han-Sol Jeong verfasserin aut Su-Jung Park verfasserin aut Yeongmu Jeong verfasserin aut Dongwan Kang verfasserin aut Jeongin Ko verfasserin aut SangGyun Noh verfasserin aut Hae Young Chung verfasserin aut Hyung Ryong Moon verfasserin aut Seong Hoon Yoon verfasserin aut In Experimental Hematology & Oncology BMC, 2012 11(2022), 1, Seite 12 (DE-627)718833341 (DE-600)2669066-4 21623619 nnns volume:11 year:2022 number:1 pages:12 https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/article/a199f05f9eec470bbb79bf94c554eaad kostenfrei https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/toc/2162-3619 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 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 11 2022 1 12
allfieldsSound	10.1186/s40164-022-00324-8 doi (DE-627)DOAJ08445279X (DE-599)DOAJa199f05f9eec470bbb79bf94c554eaad DE-627 ger DE-627 rakwb eng RC633-647.5 RC254-282 Jae Heun Chung verfasserin aut MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment. Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein Diseases of the blood and blood-forming organs Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ho Jung Choi verfasserin aut Yong Jung Kang verfasserin aut Yun Seong Kim verfasserin aut Sang-Yull Lee verfasserin aut Ryuk Jun Kwon verfasserin aut Han-Sol Jeong verfasserin aut Su-Jung Park verfasserin aut Yeongmu Jeong verfasserin aut Dongwan Kang verfasserin aut Jeongin Ko verfasserin aut SangGyun Noh verfasserin aut Hae Young Chung verfasserin aut Hyung Ryong Moon verfasserin aut Seong Hoon Yoon verfasserin aut In Experimental Hematology & Oncology BMC, 2012 11(2022), 1, Seite 12 (DE-627)718833341 (DE-600)2669066-4 21623619 nnns volume:11 year:2022 number:1 pages:12 https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/article/a199f05f9eec470bbb79bf94c554eaad kostenfrei https://doi.org/10.1186/s40164-022-00324-8 kostenfrei https://doaj.org/toc/2162-3619 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 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 11 2022 1 12
language	English
source	In Experimental Hematology & Oncology 11(2022), 1, Seite 12 volume:11 year:2022 number:1 pages:12
sourceStr	In Experimental Hematology & Oncology 11(2022), 1, Seite 12 volume:11 year:2022 number:1 pages:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein Diseases of the blood and blood-forming organs Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Experimental Hematology & Oncology
authorswithroles_txt_mv	Jae Heun Chung @@aut@@ Ho Jung Choi @@aut@@ Yong Jung Kang @@aut@@ Yun Seong Kim @@aut@@ Sang-Yull Lee @@aut@@ Ryuk Jun Kwon @@aut@@ Han-Sol Jeong @@aut@@ Su-Jung Park @@aut@@ Yeongmu Jeong @@aut@@ Dongwan Kang @@aut@@ Jeongin Ko @@aut@@ SangGyun Noh @@aut@@ Hae Young Chung @@aut@@ Hyung Ryong Moon @@aut@@ Seong Hoon Yoon @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	718833341
id	DOAJ08445279X
language_de	englisch
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callnumber-first	R - Medicine
author	Jae Heun Chung
spellingShingle	Jae Heun Chung misc RC633-647.5 misc RC254-282 misc Lung cancer misc MHY4571 misc Carcinogenesis misc Cyclic AMP-Dependent Protein Kinases misc cAMP response element-binding protein misc Diseases of the blood and blood-forming organs misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer
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topic_title	RC633-647.5 RC254-282 MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer Lung cancer MHY4571 Carcinogenesis Cyclic AMP-Dependent Protein Kinases cAMP response element-binding protein
topic	misc RC633-647.5 misc RC254-282 misc Lung cancer misc MHY4571 misc Carcinogenesis misc Cyclic AMP-Dependent Protein Kinases misc cAMP response element-binding protein misc Diseases of the blood and blood-forming organs misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC633-647.5 misc RC254-282 misc Lung cancer misc MHY4571 misc Carcinogenesis misc Cyclic AMP-Dependent Protein Kinases misc cAMP response element-binding protein misc Diseases of the blood and blood-forming organs misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC633-647.5 misc RC254-282 misc Lung cancer misc MHY4571 misc Carcinogenesis misc Cyclic AMP-Dependent Protein Kinases misc cAMP response element-binding protein misc Diseases of the blood and blood-forming organs misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer
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title_full	MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer
author_sort	Jae Heun Chung
journal	Experimental Hematology & Oncology
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author_browse	Jae Heun Chung Ho Jung Choi Yong Jung Kang Yun Seong Kim Sang-Yull Lee Ryuk Jun Kwon Han-Sol Jeong Su-Jung Park Yeongmu Jeong Dongwan Kang Jeongin Ko SangGyun Noh Hae Young Chung Hyung Ryong Moon Seong Hoon Yoon
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author-letter	Jae Heun Chung
doi_str_mv	10.1186/s40164-022-00324-8
author2-role	verfasserin
title_sort	mhy4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the pka-camp-response element-binding protein pathway in squamous cell lung cancer
callnumber	RC633-647.5
title_auth	MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer
abstract	Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.
abstractGer	Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.
abstract_unstemmed	Abstract Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (< 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.
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title_short	MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer
url	https://doi.org/10.1186/s40164-022-00324-8 https://doaj.org/article/a199f05f9eec470bbb79bf94c554eaad https://doaj.org/toc/2162-3619
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author2	Ho Jung Choi Yong Jung Kang Yun Seong Kim Sang-Yull Lee Ryuk Jun Kwon Han-Sol Jeong Su-Jung Park Yeongmu Jeong Dongwan Kang Jeongin Ko SangGyun Noh Hae Young Chung Hyung Ryong Moon Seong Hoon Yoon
author2Str	Ho Jung Choi Yong Jung Kang Yun Seong Kim Sang-Yull Lee Ryuk Jun Kwon Han-Sol Jeong Su-Jung Park Yeongmu Jeong Dongwan Kang Jeongin Ko SangGyun Noh Hae Young Chung Hyung Ryong Moon Seong Hoon Yoon
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up_date	2024-07-03T23:05:32.854Z
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MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer

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