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

Autor: Chung KS; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea., Yoo CB; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea., Lee JH; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea.; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea., Lee HH; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea., Park SE; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea.; Department of Biomedical and Pharmaceutical Sciences, College of Pharmarcy, Kyung Hee University, Seoul 02447, Korea., Han HS; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea.; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea., Lee SY; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea.; Department of Biomedical and Pharmaceutical Sciences, College of Pharmarcy, Kyung Hee University, Seoul 02447, Korea., Kwon BM; Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea., Choi JH; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea.; Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea., Lee KT; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea.; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul 02447, Korea.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2021 Oct 26; Vol. 13 (11). Date of Electronic Publication: 2021 Oct 26.
DOI: 10.3390/pharmaceutics13111794
Abstrakt: 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 c release into the cytosol, (4) loss of mitochondrial membrane potential (Δ Ψ m ), 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.
Databáze: MEDLINE
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