Hispolon induces apoptosis through JNK1/2-mediated activation of a caspase-8, -9, and -3-dependent pathway in acute myeloid leukemia (AML) cells and inhibits AML xenograft tumor growth in vivo
Journal
Journal of Agricultural and Food Chemistry
Journal Volume
61
Journal Issue
42
Pages
10063-10073
Date Issued
2013
Author(s)
Hsiao, P.-C.
Hsieh, Y.-H.
Chow, J.-M.
Yang, S.-F.
Hsiao, M.
Lin, C.-H.
Chen, H.-Y.
Chien, M.-H.
Abstract
Hispolon is an active phenolic compound of Phellinus igniarius, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML. ? 2013 American Chemical Society.
Subjects
acute myeloid leukemia; apoptosis; caspase; hispolon; JNK1/2; xenograft tumor
SDGs
Other Subjects
Cell culture; Cell death; Cell proliferation; Chemical activation; Diseases; Mammals; Acute myeloid leukemia; Antioxidant and anticancer activities; Caspases; hispolon; JNK1/2; Molecular mechanism; Phellinus igniarius; Sustained activation; Tumors; Basidiomycota; Mus; Phellinus igniarius; caspase 3; caspase 8; caspase 9; catechol derivative; hispolon; mitogen activated protein kinase 9; protein bcl 2; stress activated protein kinase 1; acute granulocytic leukemia; Agaricales; animal; apoptosis; article; cancer transplantation; cell proliferation; cell strain HL 60; chemistry; down regulation; drug effect; enzymology; genetics; human; male; metabolism; mouse; pathophysiology; SCID mouse; Agaricales; Animals; Apoptosis; Caspase 3; Caspase 8; Caspase 9; Catechols; Cell Proliferation; Down-Regulation; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; Male; Mice; Mice, SCID; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; Neoplasm Transplantation; Proto-Oncogene Proteins c-bcl-2
Type
journal article