PMID- 30580504
OWN - NLM
STAT- MEDLINE
DCOM- 20190415
LR  - 20190415
IS  - 0304-4920 (Print)
IS  - 0304-4920 (Linking)
VI  - 61
IP  - 6
DP  - 2018 Dec 31
TI  - Exploration of Niflumic Acid's Action on Ca(2)(+) Movement and Cell Viability in 
      Human Osteosarcoma Cells.
PG  - 341-348
LID - CJP.2018.BAH635 [pii]
LID - 10.4077/CJP.2018.BAH635 [doi]
AB  - Niflumic acid, a drug used for joint and muscular pain, affected Ca(2)(+) signaling 
      in different models. However, the effect of niflumic acid on Ca(2)(+) homeostasis and 
      Ca(2)(+)-related physiology in human osteosarcoma cells is unknown. This study 
      examined the effect of niflumic acid on cytosolic free Ca(2)(+) concentrations 
      ([Ca(2)(+)]i) in MG63 human osteosarcoma cells. Intracellular Ca(2)(+) concentrations in 
      suspended cells were monitored by using the fluorescent Ca(2)(+)-sensitive dye fura- 
      2. Cell viability was examined by using 
      4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio- 1,3-benzene disulfonate] 
      water soluble tetrazolium-1 (WST-1). In MG63 cells, niflumic acid at 
      concentrations of 250-750 muM evoked [Ca(2)(+)]i rises concentration-dependently. 
      Niflumic acid-evoked Ca(2)(+) entry was confirmed by Mn(2)(+)-induced quenching of fura-2 
      fluorescence. This entry was inhibited by nifedipine, econazole, SKF96365, the 
      protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA), but was 
      not affected by the PKC inhibitor GF109203X. In Ca(2)(+)- free medium, treatment with 
      the endoplasmic reticulum Ca(2)(+) pump inhibitor thapsigargin (TG) inhibited 
      niflumic acid-evoked [Ca(2)(+)]i rises. Conversely, treatment with niflumic acid 
      abolished TG-evoked [Ca(2)(+)]i rises. Inhibition of phospholipase C (PLC) with 
      U73122 also partly reduced niflumic acid-evoked [Ca(2)(+)]i rises. Niflumic acid 
      killed cells at 200-500 muM in a concentration-dependent fashion. Chelating 
      cytosolic Ca(2)(+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/ AM 
      (BAPTA/AM) did not reverse niflumic acid-induced cytotoxicity. Collectively, our 
      data suggest that in MG63 cells, niflumic acid induced [Ca(2)(+)]i rises by evoking 
      PLC-dependent Ca(2)(+) release from the endoplasmic reticulum, and Ca(2)(+) entry via 
      PKC-sensitive store-operated Ca(2)(+) entry. Niflumic acid also induced 
      Ca(2)(+)-independent cell death.
FAU - Liao, Wei-Chuan
AU  - Liao WC
AD  - Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, 
      Taiwan, Republic of China.
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 61363, Taiwan, Republic of China.
FAU - Liang, Wei-Zhe
AU  - Liang WZ
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 81362, Taiwan, Republic of China.
AD  - Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of 
      China.
FAU - Hao, Lyh-Jyh
AU  - Hao LJ
AD  - Department of Metabolism, Kaohsiung Veterans General Hospital Tainan Branch, 
      Tainan 71051, Taiwan, Republic of China.
FAU - Kuo, Chun-Chi
AU  - Kuo CC
AD  - Department of Nursing, Tzu Hui Institute of Technology, Pingtung 92641, Taiwan, 
      Republic of China.
FAU - Lin, Ko-Long
AU  - Lin KL
AD  - Department of Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung 
      81362, Taiwan, Republic of China.
FAU - Wang, Jue-Long
AU  - Wang JL
AD  - Department of Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung 
      81362, Taiwan, Republic of China.
FAU - Jan, Chung-Ren
AU  - Jan CR
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 81362, Taiwan, Republic of China.
LA  - eng
GR  - VGHKS104-095/Kaohsiung Veterans General Hospital/International
GR  - VGHKS107-169/Kaohsiung Veterans General Hospital/International
PT  - Journal Article
PL  - India
TA  - Chin J Physiol
JT  - The Chinese journal of physiology
JID - 7804502
RN  - 4U5MP5IUD8 (Niflumic Acid)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Apoptosis
MH  - *Bone Neoplasms
MH  - Calcium
MH  - Calcium Signaling
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Humans
MH  - Niflumic Acid
MH  - *Osteosarcoma
MH  - Type C Phospholipases
OTO - NOTNLM
OT  - Ca(2)(+)
OT  - endoplasmic reticulum
OT  - human osteosarcoma cells
OT  - niflumic acid
OT  - viability
COIS- The authors declared no conflicts of interest.
EDAT- 2018/12/26 06:00
MHDA- 2019/04/16 06:00
CRDT- 2018/12/25 06:00
PHST- 2018/12/25 06:00 [entrez]
PHST- 2018/12/26 06:00 [pubmed]
PHST- 2019/04/16 06:00 [medline]
AID - CJP.2018.BAH635 [pii]
AID - 10.4077/CJP.2018.BAH635 [doi]
PST - ppublish
SO  - Chin J Physiol. 2018 Dec 31;61(6):341-348. doi: 10.4077/CJP.2018.BAH635.