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Ouabain Induces Apoptotic Cell Death Through Caspase- and Mitochondria-dependent Pathways in Human Osteosarcoma U-2 OS Cells.

Abstract Ouabain, a plant-derived product/substance with Na+/K+-ATPase inhibiting properties, has been shown to exert anti-cancer activity on human cancer cells. This is the first study to investigate the effect of ouabain on apoptotic cell death of human osteosarcoma-derived U-2 OS cells.
PMID
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Authors

Mayor MeshTerms
Keywords

Ouabain

apoptosis

caspase-dependent pathways

human osteosarcoma U-2 OS cells

mitochondria-dependent pathways

Journal Title anticancer research
Publication Year Start




PMID- 29277770
OWN - NLM
STAT- In-Process
LR  - 20171226
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 38
IP  - 1
DP  - 2018 Jan
TI  - Ouabain Induces Apoptotic Cell Death Through Caspase- and Mitochondria-dependent 
      Pathways in Human Osteosarcoma U-2 OS Cells.
PG  - 169-178
AB  - BACKGROUND/AIM: Ouabain, a plant-derived product/substance with Na(+)/K(+)-ATPase
      inhibiting properties, has been shown to exert anti-cancer activity on human
      cancer cells. This is the first study to investigate the effect of ouabain on
      apoptotic cell death of human osteosarcoma-derived U-2 OS cells. MATERIALS AND
      METHODS: Flow cytometry was used to examine cell viability, cell cycle, and
      reactive oxygen species (ROS), Ca(2+), mitochondrial membrane potential (MMP) and
      caspase activity. Morphological changes were examined by contrast-phase
      microscopy, while apoptosis-associated protein levels were analyzed by western
      blot. RESULTS: Ouabain, at concentrations of 5-60 muM, significantly decreased
      the total viable cells and induced cell morphological changes in a time-dependent
      manner. It also time-dependently decreased G0/G1 phase and increased S and G2/M
      phase in U-2 OS cells. The production of ROS and the levels of MMPs (DeltaPsim)
      were inhibited, while Ca(2+) production in U-2 OS cells was increased. Regarding 
      cell apoptosis, flow cytometry assay revealed increased caspase-3, -8, and -9
      activities in U-2 OS cells. Moreover, western blot results showed that ouabain
      increased the expression of pro-apoptotic protein Bax and decreased the
      expression of anti-apoptotic protein Bcl-2 in U-2 OS cells. Furthermore, results 
      also showed that ouabain increased cytochrome c release, apoptosis-inducing
      factor (AIF) and endonuclease (Endo) G that is associated with apoptosis through 
      caspase-dependent and -independent pathway in U-2 OS cells. CONCLUSION: Our
      findings provide important insight into the cytotoxic effects of ouabain on U-2
      OS cells, in vitro, which are mediated at least partly via cell apoptosis
      induction.
CI  - Copyright(c) 2018, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Chou, Wen-Hsiang
AU  - Chou WH
AD  - School of Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.
AD  - Department of Orthopedics, Cheng Hsin General Hospital, Taipei, Taiwan, R.O.C.
AD  - Department of Information Management, St. Mary's Junior College of Medicine,
      Nursing and Management, Yilan, Taiwan, R.O.C.
FAU - Liu, Ko-Lin
AU  - Liu KL
AD  - Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial
      Hospital, Taipei, Taiwan, R.O.C.
FAU - Shih, Yung-Luen
AU  - Shih YL
AD  - Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial
      Hospital, Taipei, Taiwan, R.O.C.
AD  - School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei
      City, Taiwan, R.O.C.
FAU - Chuang, Ying-Ying
AU  - Chuang YY
AD  - Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan,
      R.O.C.
FAU - Chou, Jason
AU  - Chou J
AD  - Department of Anatomic Pathology, Cheng Hsin General Hospital, Taipei, Taiwan,
      R.O.C.
FAU - Lu, Hsu-Feng
AU  - Lu HF
AD  - Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan,
      R.O.C.
AD  - Department of Restaurant, Hotel and Institutional Management, Fu-Jen Catholic
      University, New Taipei City, Taiwan, R.O.C.
FAU - Jair, Herng-Woei
AU  - Jair HW
AD  - Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan,
      R.O.C.
FAU - Lee, Ming-Zhe
AU  - Lee MZ
AD  - Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan,
      R.O.C.
FAU - Au, Man-Kuan
AU  - Au MK
AD  - Department of Orthopedics, Cheng Hsin General Hospital, Taipei, Taiwan, R.O.C.
      [email protected] [email protected]
FAU - Chung, Jing-Gung
AU  - Chung JG
AD  - Department of Biological Science and Technology, China Medical University,
      Taichung, Taiwan, R.O.C. [email protected] [email protected]
AD  - Department of Biotechnology, Asia University, Taichung, Taiwan, R.O.C.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
OTO - NOTNLM
OT  - Ouabain
OT  - apoptosis
OT  - caspase-dependent pathways
OT  - human osteosarcoma U-2 OS cells
OT  - mitochondria-dependent pathways
EDAT- 2017/12/27 06:00
MHDA- 2017/12/27 06:00
CRDT- 2017/12/27 06:00
PHST- 2017/09/22 00:00 [received]
PHST- 2017/10/25 00:00 [revised]
PHST- 2017/10/30 00:00 [accepted]
PHST- 2017/12/27 06:00 [entrez]
PHST- 2017/12/27 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
AID - 38/1/169 [pii]
PST - ppublish
SO  - Anticancer Res. 2018 Jan;38(1):169-178.