Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway

Jeong-Hyeon Ko
,
Jae Hwi Lee
,
Sang Hoon Jung
,
Seok-Geun Lee
ORCID logo ,
Arunachalam Chinnathambi
,
Sulaiman Ali Alharbi
,
Woong Mo Yang
,
Jae-Young Um
,
Gautam Sethi
* ,
Kwang Seok Ahn
* ORCID logo
Version 1 : Received: 29 June 2017 / Approved: 29 June 2017 / Online: 29 June 2017 (08:40:36 CEST)

A peer-reviewed article of this Preprint also exists.

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. 2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway. Molecules 2017, 22, 1157. 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. 2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway. Molecules 2017, 22, 1157.

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.

Keywords

2,5-Dihydroxyacetophenone; multiple myeloma; MAPK; apoptosis

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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