Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells

The present study demonstrated that 2′-hydroxycinnamaldehyde (2′-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expres...

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Autores principales:	Kyung-Sook Chung, Chae-Bin Yoo, Jeong-Hun Lee, Hwi-Ho Lee, Sang-Eun Park, Hee-Soo Han, Su-Yeon Lee, Byoung-Mok Kwon, Jung-Hye Choi, Kyung-Tae Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	2′-hydroxycinnamaldehyde reactive oxygen species (ROS) Bim Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/fe677e391a9f4ab097880eb97737028d
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spelling	oai:doaj.org-article:fe677e391a9f4ab097880eb97737028d2021-11-25T18:40:44ZRegulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells10.3390/pharmaceutics131117941999-4923https://doaj.org/article/fe677e391a9f4ab097880eb97737028d2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1794https://doaj.org/toc/1999-4923The present study demonstrated that 2′-hydroxycinnamaldehyde (2′-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expression, (3) cytochrome <i>c</i> release into the cytosol, (4) loss of mitochondrial membrane potential (Δ<i>Ψ<sub>m</sub></i>), and (5) caspase activation. 2′-HCA also induced the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase1/2 (ERK1/2) in HL-60 cells. The pharmacological and genetic inhibition of JNK effectively prevented 2′-HCA-induced apoptosis and activator protein-1 (AP-1)-DNA binding. In addition, 2′-HCA resulted in the accumulation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH) and protein thiols (PSH) in HL-60 cells. NAC treatment abrogated 2′-HCA-induced JNK phosphorylation, AP-1-DNA binding, and Bim mitochondrial translocation, suggesting that oxidative stress may be required for 2′-HCA-induced intrinsic apoptosis. Xenograft mice inoculated with HL-60 leukemia cells demonstrated that the intraperitoneal administration of 2′-HCA inhibited tumor growth by increasing of TUNEL staining, the expression levels of nitrotyrosine and pro-apoptotic proteins, but reducing of PCNA protein expression. Taken together, our findings suggest that 2′-HCA induces apoptosis via the ROS-dependent JNK pathway and could be considered as a potential therapeutic agent for leukemia.Kyung-Sook ChungChae-Bin YooJeong-Hun LeeHwi-Ho LeeSang-Eun ParkHee-Soo HanSu-Yeon LeeByoung-Mok KwonJung-Hye ChoiKyung-Tae LeeMDPI AGarticle2′-hydroxycinnamaldehydereactive oxygen species (ROS)BimPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1794, p 1794 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	2′-hydroxycinnamaldehyde reactive oxygen species (ROS) Bim Pharmacy and materia medica RS1-441
spellingShingle	2′-hydroxycinnamaldehyde reactive oxygen species (ROS) Bim Pharmacy and materia medica RS1-441 Kyung-Sook Chung Chae-Bin Yoo Jeong-Hun Lee Hwi-Ho Lee Sang-Eun Park Hee-Soo Han Su-Yeon Lee Byoung-Mok Kwon Jung-Hye Choi Kyung-Tae Lee Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells
description	The present study demonstrated that 2′-hydroxycinnamaldehyde (2′-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expression, (3) cytochrome <i>c</i> release into the cytosol, (4) loss of mitochondrial membrane potential (Δ<i>Ψ<sub>m</sub></i>), and (5) caspase activation. 2′-HCA also induced the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase1/2 (ERK1/2) in HL-60 cells. The pharmacological and genetic inhibition of JNK effectively prevented 2′-HCA-induced apoptosis and activator protein-1 (AP-1)-DNA binding. In addition, 2′-HCA resulted in the accumulation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH) and protein thiols (PSH) in HL-60 cells. NAC treatment abrogated 2′-HCA-induced JNK phosphorylation, AP-1-DNA binding, and Bim mitochondrial translocation, suggesting that oxidative stress may be required for 2′-HCA-induced intrinsic apoptosis. Xenograft mice inoculated with HL-60 leukemia cells demonstrated that the intraperitoneal administration of 2′-HCA inhibited tumor growth by increasing of TUNEL staining, the expression levels of nitrotyrosine and pro-apoptotic proteins, but reducing of PCNA protein expression. Taken together, our findings suggest that 2′-HCA induces apoptosis via the ROS-dependent JNK pathway and could be considered as a potential therapeutic agent for leukemia.
format	article
author	Kyung-Sook Chung Chae-Bin Yoo Jeong-Hun Lee Hwi-Ho Lee Sang-Eun Park Hee-Soo Han Su-Yeon Lee Byoung-Mok Kwon Jung-Hye Choi Kyung-Tae Lee
author_facet	Kyung-Sook Chung Chae-Bin Yoo Jeong-Hun Lee Hwi-Ho Lee Sang-Eun Park Hee-Soo Han Su-Yeon Lee Byoung-Mok Kwon Jung-Hye Choi Kyung-Tae Lee
author_sort	Kyung-Sook Chung
title	Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells
title_short	Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells
title_full	Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells
title_fullStr	Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells
title_full_unstemmed	Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells
title_sort	regulation of ros-dependent jnk pathway by 2’-hydroxycinnamaldehyde inducing apoptosis in human promyelocytic hl-60 leukemia cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fe677e391a9f4ab097880eb97737028d
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Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells

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