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Title: 2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway
Authors: Ko, J.-H
Lee, J.H
Jung, S.H
Lee, S.-G
Chinnathambi, A
Alharbi, S.A
Yang, W.M
Um, J.-Y
Sethi, G 
Ahn, K.S
Keywords: acetophenone derivative
antineoplastic agent
mitogen activated protein kinase
cell proliferation
drug effects
gene expression
M phase cell cycle checkpoint
MAPK signaling
multiple myeloma
tumor cell line
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Gene Expression
M Phase Cell Cycle Checkpoints
MAP Kinase Signaling System
Mitogen-Activated Protein Kinases
Multiple Myeloma
Issue Date: 2017
Citation: Ko, J.-H, Lee, J.H, Jung, S.H, Lee, S.-G, Chinnathambi, A, Alharbi, S.A, Yang, W.M, Um, J.-Y, Sethi, G, Ahn, K.S (2017). 2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway. Molecules (Basel, Switzerland) 22 (7). ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: 2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation and induced apoptosis, as characterized by the cleavage of PARP and the activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein kinase (MAPK) pathways have been linked to the modulation of the angiogenesis, proliferation, metastasis, and invasion of tumors. We therefore attempted to determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma.
Source Title: Molecules (Basel, Switzerland)
ISSN: 14203049
DOI: 10.3390/molecules22071157
Rights: Attribution 4.0 International
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