PMID- 25106108
OWN - NLM
STAT- MEDLINE
DCOM- 20150205
LR  - 20141202
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 221
DP  - 2014 Sep 25
TI  - The mechanism of honokiol-induced intracellular Ca(2+) rises and apoptosis in 
      human glioblastoma cells.
PG  - 13-23
LID - S0009-2797(14)00227-0 [pii]
LID - 10.1016/j.cbi.2014.07.012 [doi]
AB  - Honokiol, an active constituent of oriental medicinal herb Magnolia officinalis, 
      caused Ca(2+) mobilization and apoptosis in different cancer cells. In vivo, 
      honokiol crossed the blood-brain or -cerebrospinal fluid barrier, suggesting that 
      it may be an effective drug for the treatment of brain tumors, including 
      glioblastoma. This study examined the effect of honokiol on intracellular Ca(2+) 
      concentration ([Ca(2+)]i) and apoptosis in DBTRG-05MG human glioblastoma cells. 
      Honokiol concentration-dependently induced a [Ca(2+)]i rise. The signal was 
      decreased partially by removal of extracellular Ca(2+). Honokiol-triggered 
      [Ca(2+)]i rise was not suppressed by store-operated Ca(2+) channel blockers 
      (nifedipine, econazole, SK&F96365) and the protein kinase C (PKC) activator 
      phorbol 12-myristate 13 acetate (PMA), but was inhibited by the PKC inhibitor 
      GF109203X. GF109203X-induced inhibition was not altered by removal of 
      extracellular Ca(2+). In Ca(2+)-free medium, pretreatment with the endoplasmic 
      reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 
      2,5-di-tert-butylhydroquinone (BHQ) abolished honokiol-induced [Ca(2+)]i rise. 
      Conversely, incubation with honokiol abolished TG or BHQ-induced [Ca(2+)]i rise. 
      Inhibition of phospholipase C (PLC) with U73122 abolished honokiol-induced 
      [Ca(2+)]i rise. Honokiol (20-80muM) reduced the cell viability, which was not 
      reversed by prechelating cytosolic Ca(2+) with BAPTA-AM 
      (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester). 
      Honokiol (20-60muM) enhanced reactive oxygen species (ROS) production, decreased 
      mitochondrial membrane potential, released cytochrome c, and activated 
      caspase-9/caspase-3. Together, honokiol induced a [Ca(2+)]i rise by inducing 
      PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via 
      PKC-dependent, non store-operated Ca(2+) channels. Moreover, honokiol activated 
      the mitochondrial pathway of apoptosis in DBTRG-05MG human glioblastoma cells.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Liang, Wei-Zhe
AU  - Liang WZ
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 813, Taiwan, ROC.
FAU - Chou, Chiang-Ting
AU  - Chou CT
AD  - Department of Nursing, Division of Basic Medical Sciences, Chang Gung University 
      of Science and Technology, Chia-Yi 613, Taiwan, ROC; Chronic Diseases and Health 
      Promotion Research Center, Chang Gung University of Science and Technology, 
      Chia-Yi 613, Taiwan, ROC.
FAU - Chang, Hong-Tai
AU  - Chang HT
AD  - Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, 
      Taiwan, ROC.
FAU - Cheng, Jin-Shiung
AU  - Cheng JS
AD  - Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, 
      Taiwan, ROC.
FAU - Kuo, Daih-Huang
AU  - Kuo DH
AD  - Department of Pharmacy, Tajen University, Pingtung 907, Taiwan, ROC.
FAU - Ko, Kuang-Chung
AU  - Ko KC
AD  - Department of Gastroenterology, Kaohsiung Veterans General Hospital-Pingtung 
      Branch 912, Taiwan, ROC.
FAU - Chiang, Ni-Na
AU  - Chiang NN
AD  - Department of Pharmacy, Kaohsiung Veterans General Hospital-Pingtung Branch 912, 
      Taiwan, ROC.
FAU - Wu, Ru-Fang
AU  - Wu RF
AD  - Department of Pharmacy, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, 
      Kaohsiung 802, Taiwan, ROC.
FAU - Shieh, Pochuen
AU  - Shieh P
AD  - Department of Pharmacy, Tajen University, Pingtung 907, Taiwan, ROC.
FAU - Jan, Chung-Ren
AU  - Jan CR
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 813, Taiwan, ROC. Electronic address: pseudoo67@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140807
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Estrenes)
RN  - 0 (Lignans)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyrrolidinones)
RN  - 112648-68-7 
      (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione)
RN  - 11513CCO0N (honokiol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Apoptosis/drug effects
MH  - Biphenyl Compounds/*pharmacology
MH  - Calcium/*analysis
MH  - Calcium Signaling/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Estrenes/pharmacology
MH  - Glioblastoma/physiopathology
MH  - Homeostasis
MH  - Humans
MH  - Lignans/*pharmacology
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Pyrrolidinones/pharmacology
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Apoptosis
OT  - Ca(2+)
OT  - Honokiol
OT  - Human glioblastoma cells
OT  - Mitochondrial membrane potential
EDAT- 2014/08/12 06:00
MHDA- 2015/02/06 06:00
CRDT- 2014/08/10 06:00
PHST- 2013/11/29 00:00 [received]
PHST- 2014/07/15 00:00 [revised]
PHST- 2014/07/25 00:00 [accepted]
PHST- 2014/08/10 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/02/06 06:00 [medline]
AID - S0009-2797(14)00227-0 [pii]
AID - 10.1016/j.cbi.2014.07.012 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2014 Sep 25;221:13-23. doi: 10.1016/j.cbi.2014.07.012. Epub 
      2014 Aug 7.