PMID- 24627159
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20140404
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 31
IP  - 5
DP  - 2014 May
TI  - Arsenic hexoxide enhances TNF-alpha-induced anticancer effects by inhibiting NF-kappaB 
      activity at a safe dose in MCF-7 human breast cancer cells.
PG  - 2305-11
LID - 10.3892/or.2014.3085 [doi]
AB  - Arsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of 
      cancer since the late 1980s. Evidence suggests that the anticancer effects of 
      As4O6 are different from those of As2O3. Tumor necrosis factor-alpha (TNF-alpha) is 
      generally increased in advanced cancer and is closely related to cancer 
      progression, although it has cancer-killing effects. The reason is that TNF-alpha 
      activates nuclear factor-kappaB (NF-kappaB) that is involved in cell proliferation, 
      invasion, drug resistance and metastasis. In the present study, we investigated 
      the effects of As4O6 on NF-kappaB activity, NF-kappaB-mediated cellular responses, and 
      NF-kappaB-regulated gene expressions involved in metastasis at the concentrations of 
      As4O6 where no cytotoxicity was observed. As4O6 suppressed NF-kappaB activation in 
      both TNF-alpha-treated and control cells, and also suppressed IkappaB phosphorylation in 
      a time-dependent manner, suggesting the suppression of NF-kappaB results, in part, 
      from the inhibition of IkappaB degradation. We also confirmed the anti-NF-kappaB activity 
      of As4O6 with synergism with TNF-alpha by augmenting caspase-8 activation. As4O6 also 
      suppressed NF-kappaB activation induced by TNF-alpha, and some of the downstream 
      NF-kappaB-regulated proteins involved in cancer proliferation, anti-apoptosis and 
      metastasis. In conclusion, the present study demonstrated that As4O6 has 
      anticancer properties by inhibiting NF-kappaB activation and NF-kappaB-regulated proteins 
      at least in part through the inhibition of IkappaB phosphorylation, especially in the 
      conditions of advanced cancer where TNF-alpha is highly secreted.
FAU - Kim, Min Jeong
AU  - Kim MJ
AD  - Department of Internal Medicine, Institute of Health Sciences, Gyeongsang 
      National University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Jung, Ji Hyun
AU  - Jung JH
AD  - Department of Internal Medicine, Institute of Health Sciences, Gyeongsang 
      National University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Lee, Won Sup
AU  - Lee WS
AD  - Department of Internal Medicine, Institute of Health Sciences, Gyeongsang 
      National University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Yun, Jeong Won
AU  - Yun JW
AD  - Department of Internal Medicine, Institute of Health Sciences, Gyeongsang 
      National University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Lu, Jing Nan
AU  - Lu JN
AD  - Department of Internal Medicine, Institute of Health Sciences, Gyeongsang 
      National University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Yi, Sang Mi
AU  - Yi SM
AD  - Department of Internal Medicine, Institute of Health Sciences, Gyeongsang 
      National University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Kim, Hye Jung
AU  - Kim HJ
AD  - Department of Pharmacology, Institute of Health Sciences, Gyeongsang National 
      University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Chang, Seong-Hwan
AU  - Chang SH
AD  - Department of Surgery, Konkuk University School of Medicine, Seoul 143-701, 
      Republic of Korea.
FAU - Kim, Gon-Sup
AU  - Kim GS
AD  - School of Veterinary Medicine and Research Institute of Life Science, Gyeongsang 
      National University, Jinju 660-701, Republic of Korea.
FAU - Hong, Soon Chan
AU  - Hong SC
AD  - Department of Surgery, Institute of Health Sciences, Gyeongsang National 
      University School of Medicine, Jinju 660-702, Republic of Korea.
FAU - Ha, Woo Song
AU  - Ha WS
AD  - Department of Surgery, Institute of Health Sciences, Gyeongsang National 
      University School of Medicine, Jinju 660-702, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140312
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Arsenicals)
RN  - 0 (Oxides)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 3.4.22.- (Caspase 8)
RN  - N712M78A8G (Arsenic)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Arsenic/pharmacology
MH  - Arsenicals/*pharmacology
MH  - Breast Neoplasms/*drug therapy
MH  - Caspase 8/biosynthesis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Drug Resistance, Neoplasm
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - MCF-7 Cells
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Oxides/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Transcription Factor RelA/*antagonists & inhibitors
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2014/03/15 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/03/15 06:00
PHST- 2014/01/22 00:00 [received]
PHST- 2014/02/28 00:00 [accepted]
PHST- 2014/03/15 06:00 [entrez]
PHST- 2014/03/15 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - 10.3892/or.2014.3085 [doi]
PST - ppublish
SO  - Oncol Rep. 2014 May;31(5):2305-11. doi: 10.3892/or.2014.3085. Epub 2014 Mar 12.