PMID- 26154615
OWN - NLM
STAT- MEDLINE
DCOM- 20151023
LR  - 20220321
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Linking)
VI  - 78
IP  - 7
DP  - 2015 Jul 24
TI  - The Mechanism of Ca(2+) Movement in the Involvement of Baicalein-Induced 
      Cytotoxicity in ZR-75-1 Human Breast Cancer Cells.
PG  - 1624-34
LID - 10.1021/acs.jnatprod.5b00173 [doi]
AB  - Baicalein (5,6,7-trihydroxyflavone) (1) has been found to be active against a 
      wide variety of cancer cells. However, the molecular mechanism underlying the 
      effects of 1 on the induction of Ca(2+) movement and cytotoxicity in human breast 
      cancer cells is unknown. This study examined the relationship between 1-induced 
      Ca(2+) signaling and cytotoxicity in ZR-75-1 human breast cancer cells. The in 
      vitro investigations reported herein produced the following results: (i) Compound 
      1 increased intracellular Ca(2+) concentration ([Ca(2+)]i) in a 
      concentration-dependent manner. The signal was decreased by approximately 50% by 
      removal of extracellular Ca(2+). (ii) Compound 1-triggered [Ca(2+)]i increases 
      were significantly suppressed by store-operated Ca(2+) channel blockers 
      2-aminoethoxydiphenyl borate (2-APB) and the PKC inhibitor GF109203X. (iii) In 
      Ca(2+)-free medium, compound 1-induced [Ca(2+)]i increases were also inhibited by 
      GF109203X. Furthermore, pretreatment with the endoplasmic reticulum Ca(2+) pump 
      inhibitor thapsigargin (TG) or 2,5-ditert-butylhydroquinone (BHQ) abolished 
      1-induced [Ca(2+)]i increases. Inhibition of phospholipase C (PLC) with U73122 
      abolished 1-induced [Ca(2+)]i increases. (iv) Compound 1 (20-40 muM) caused 
      cytotoxicity, increased reactive oxygen species (ROS) production, and activated 
      caspase-9/caspase-3. Furthermore, compound 1-induced apoptosis was significantly 
      inhibited by prechelating cytosolic Ca(2+) with BAPTA-AM 
      (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester) or 
      by decreasing ROS with the antioxidant NAC (N-acetylcysteine). Together, 
      baicalein (1) induced a [Ca(2+)]i increase by inducing PLC-dependent Ca(2+) 
      release from the endoplasmic reticulum and Ca(2+) entry via PKC-dependent, 
      2-APB-sensitive store-operated Ca(2+) channels. Moreover, baicalein (1) induced 
      Ca(2+)-associated apoptosis involved ROS production in ZR-75-1 cells.
FAU - Chang, Hong-Tai
AU  - Chang HT
AD  - daggerDepartment of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, 
      Taiwan, Republic of China.
FAU - Chou, Chiang-Ting
AU  - Chou CT
AD  - double daggerDepartment of Nursing, Division of Basic Medical Sciences, Chang Gung University 
      of Science and Technology, Chia-Yi 613, Taiwan, Republic of China.
AD  -  section signChronic Diseases and Health Promotion Research Center, Chang Gung University of 
      Science and Technology, Chia-Yi 613, Taiwan, Republic of China.
FAU - Kuo, Daih-Huang
AU  - Kuo DH
AD  -  perpendicularDepartment of Pharmacy, Tajen University, Pingtung 907, Taiwan, Republic of 
      China.
FAU - Shieh, Pochuen
AU  - Shieh P
AD  -  perpendicularDepartment of Pharmacy, Tajen University, Pingtung 907, Taiwan, Republic of 
      China.
FAU - Jan, Chung-Ren
AU  - Jan CR
AD  -  parallelDepartment of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, 386 Ta-Chung 1st Road, Kaohsiung 813, Taiwan, Republic of China.
FAU - Liang, Wei-Zhe
AU  - Liang WZ
AD  -  parallelDepartment of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, 386 Ta-Chung 1st Road, Kaohsiung 813, Taiwan, Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150708
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Boron Compounds)
RN  - 0 (Flavanones)
RN  - 0 (Indoles)
RN  - 0 (Maleimides)
RN  - 0 (Reactive Oxygen Species)
RN  - 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid 
      acetoxymethyl ester)
RN  - 49QAH60606 (baicalein)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - E4ES684O93 (2-aminoethoxydiphenyl borate)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
RN  - L79H6N0V6C (bisindolylmaleimide I)
RN  - SY7Q814VUP (Calcium)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Boron Compounds
MH  - Breast Neoplasms
MH  - Calcium/*metabolism
MH  - Caspase 3/metabolism
MH  - Caspase 9
MH  - Cytosol/metabolism
MH  - Egtazic Acid/analogs & derivatives
MH  - Endoplasmic Reticulum/drug effects
MH  - Female
MH  - Flavanones/*pharmacology
MH  - Humans
MH  - Indoles
MH  - Maleimides
MH  - Molecular Structure
MH  - Reactive Oxygen Species/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Type C Phospholipases
EDAT- 2015/07/15 06:00
MHDA- 2015/10/24 06:00
CRDT- 2015/07/09 06:00
PHST- 2015/07/09 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/10/24 06:00 [medline]
AID - 10.1021/acs.jnatprod.5b00173 [doi]
PST - ppublish
SO  - J Nat Prod. 2015 Jul 24;78(7):1624-34. doi: 10.1021/acs.jnatprod.5b00173. Epub 
      2015 Jul 8.