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A new insight into the apoptotic effect of nitidine chloride targeting Checkpoint kinase 2 in human cervical cancer in vitro

Authors
 Hye-Jeong Kwon  ;  Lee-Han Kim  ;  Chi-Hyun Ahn  ;  In-Hyoung Yang  ;  Kyoung-Ok Hong  ;  Seong Doo Hong  ;  Ji-Ae Shin  ;  Sung-Dae Cho 
Citation
 JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION, Vol.65(3) : 193-202, 2019-11 
Journal Title
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
ISSN
 0912-0009 
Issue Date
2019-11
Keywords
cervical cancer ; nitidine chloride ; Chk2 activation ; apoptosis
Abstract
Nitidine chloride (NC), a natural, bioactive, phytochemical alkaloid derived from the roots of Zanthoxylum nitidum, has been reported to exhibit anti-tumor activity against various types of cancer. However, the potential therapeutic role of NC in human cervical cancer has not yet been studied. We are the first to report that NC acts as a potential apoptosis-inducing agent for human cervical cancer in vitro. NC treatment of human cervical cancer cell lines induced caspase-mediated apoptosis, thereby reducing cell viability. Phospho-kinase proteome profiling using a human phospho-kinase array revealed that NC treatment phosphorylated Checkpoint kinase 2 (Chk2) at Thr68, which activates Chk2 in both cell lines. We also found that NC significantly affected the p53/Bim signaling axis, which was accompanied by mitochondria! membrane depolarization and cytochrome c release from the mitochondria into the cytosol. In addition, NC profoundly increased phosphorylation of the histone variant H2AX at 5er139, a typical marker of DNA damage. Taken together, these results provide in vitro evidence that NC can increase Chk2 activation, thereby acting as an attractive cell death inducer for treatment of human cervical cancer.
Files in This Item:
T9992019164.pdf Download
DOI
10.3164/jcbn.19-28
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Kim, Lee-Han(김이한)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189167
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