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

Jeong-Hyeon Ko,Gautam Sethi,Jae Hwi Lee,Kwang Seok Ahn,Arunachalam Chinnathambi,Sulaiman Ali Alharbi,Woong Mo Yang,Sang Hoon Jung,Jae-Young Um,Seok-Geun Lee

doi:10.3390/molecules22071157

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.

Highlights

Radix rehmanniae is obtained from the root of the herbaceous plant Rehmannia glutinosa Libosch
The results shown are representative of the three independent experiments; (B) The ratios of phosphorylated proteins to non-phosphorylated proteins were measured and the (B) The ratios of phosphorylated proteins to non-phosphorylated proteins were measured and the band band density values were expressed as mean ± SE; (C) U266 cells were pretreated with SP600125 density values were expressed as mean ± SE; (C) U266 cells were pretreated with SP600125 (5 μM), (5 μM), SB203580 (10 μM), or PD98059 (25 μM) for 30 min, incubated with DHAP (100 μM) for
We found that DHAP induced the activation of JNK, p38, and extracellular signal-regulated kinase (ERK), and caused substantial of proliferation, induction of apoptosis, ledintoU266 activation potentiation of bortezomib’s apoptotic and effects cells. of caspase-3, caspase-8, and caspase-9

Summary

Introduction

Radix rehmanniae is obtained from the root of the herbaceous plant Rehmannia glutinosa Libosch. It is a traditional Chinese medicinal herb and has been found to have biological properties like anti-inflammatory and wound-healing effects and the ability to attenuate diabetic nephropathy [1,2,3]. Dysregulated inflammatory responses are important in a number of chronic diseases, macrophages. Including cancer [5,6,7,8], and we responses are important in a number of chronic diseases, including cancer [5,6,7,8], and we postulate that DHAP may exhibit promising anti-cancer properties. Including cancer [5,6,7,8], and we responses are important in a number of chronic diseases, including cancer [5,6,7,8], and we postulate that DHAP may exhibit promising anti-cancer properties. postulate

Objectives

Results

Conclusion