PMID- 26193270
OWN - NLM
STAT- MEDLINE
DCOM- 20160421
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 16
IP  - 7
DP  - 2015 Jul 17
TI  - A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-kappaB/p65 
      and COX-2 Expression on Human Hepatoma Cells. Part 3.
PG  - 16401-13
LID - 10.3390/ijms160716401 [doi]
AB  - A new anticancer ligustrazine derivative, 3beta-hydroxyolea-12-en-28-oic acid- 
      3,5,6-trimethylpyrazin-2-methylester (T-OA, C38H58O3N2), was previously reported. 
      It was synthesized via conjugating hepatoprotective and anticancer ingredients of 
      traditional Chinese medicine. We found that T-OA exerted its anticancer activity 
      by preventing the expression of nuclear transcription factor NF-kappaB/p65 and COX-2 
      in S180 mice. However, the selective cytotoxicity of T-OA on various kinds of 
      cell lines has not been studied sufficiently. In the present study, compared with 
      Cisplatin, T-OA was more toxic to human hepatoma cell line Bel-7402 (IC50 = 6.36 
      +/- 1.56 microM) than other three cancer cell lines (HeLa, HT-29, BGC-823), and no 
      toxicity was observed toward Madin-Darby canine kidney cell line MDCK (IC50 > 150 
      microM). The morphological changes of Bel-7402 cells demonstrated that T-OA had an 
      apoptosis-inducing effect which had been substantiated using 
      4',6-diamidino-2-phenylindole (DAPI) staining, acridine orange (AO)/ethidium 
      bromide (EB) staining, flow cytometry and mitochondrial membrane potential assay. 
      Combining the immumohistochemical staining, we found T-OA could prevent the 
      expression of NF-kappaB/p65 and COX-2 in Bel-7402 cells. Both of the proteins have 
      been known to play roles in apoptosis and are mainly located in the nuclei. 
      Moreover subcellular localization was performed to reveal that T-OA exerts in 
      nuclei of Bel-7402 cells. The result was in accordance with the effects of 
      down-regulating the expression of NF-kappaB/p65 and COX-2.
FAU - Zhang, Chenze
AU  - Zhang C
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. zcz920418@163.com.
FAU - Yan, Wenqiang
AU  - Yan W
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. ywq3226925@163.com.
FAU - Li, Bi
AU  - Li B
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. libimegan@163.com.
FAU - Xu, Bing
AU  - Xu B
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. weichenxubing@126.com.
FAU - Gong, Yan
AU  - Gong Y
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. gongyan90@163.com.
FAU - Chu, Fuhao
AU  - Chu F
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. chufhao@163.com.
FAU - Zhang, Yuzhong
AU  - Zhang Y
AD  - Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, 
      China. zyz100102@126.com.
FAU - Yao, Qiuli
AU  - Yao Q
AD  - School of Nursing, Beijing University of Chinese Medicine, Beijing 100102, China. 
      yaoqiuli2008@163.com.
FAU - Wang, Penglong
AU  - Wang P
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. wpl581@126.com.
FAU - Lei, Haimin
AU  - Lei H
AD  - School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 
      100102, China. leihaimin@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150717
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Pyrazines)
RN  - 0 (Transcription Factor RelA)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - V80F4IA5XG (tetramethylpyrazine)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Carcinoma, Hepatocellular/*metabolism
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Dogs
MH  - HT29 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Madin Darby Canine Kidney Cells
MH  - Pyrazines/*pharmacology
MH  - Transcription Factor RelA/genetics/*metabolism
PMC - PMC4519956
OTO - NOTNLM
OT  - NF-kappaB/p65 and COX-2
OT  - hepatoma
OT  - ligustrazine derivative
OT  - selective cytotoxicity
EDAT- 2015/07/21 06:00
MHDA- 2016/04/22 06:00
PMCR- 2015/07/01
CRDT- 2015/07/21 06:00
PHST- 2015/05/14 00:00 [received]
PHST- 2015/07/03 00:00 [revised]
PHST- 2015/07/13 00:00 [accepted]
PHST- 2015/07/21 06:00 [entrez]
PHST- 2015/07/21 06:00 [pubmed]
PHST- 2016/04/22 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - ijms160716401 [pii]
AID - ijms-16-16401 [pii]
AID - 10.3390/ijms160716401 [doi]
PST - epublish
SO  - Int J Mol Sci. 2015 Jul 17;16(7):16401-13. doi: 10.3390/ijms160716401.