PMID- 20138958
OWN - NLM
STAT- MEDLINE
DCOM- 20100608
LR  - 20131121
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 320
IP  - 1-2
DP  - 2010 May 14
TI  - Iodine induces apoptosis via regulating MAPKs-related p53, p21, and Bcl-xL in 
      thyroid cancer cells.
PG  - 128-35
LID - 10.1016/j.mce.2010.02.004 [doi]
AB  - Thyroid cancer is the most common endocrine malignancy and exhibits the full 
      range of malignant behaviors from the relatively indolent occult differentiated 
      thyroid cancer to uniformly aggressive and lethal anaplastic thyroid cancer. 
      Iodine is a well known key element in thyroid normal function maintenance and 
      thyroid cancer development. However, the effects induced by iodine and the 
      molecular mechanisms involved remain poorly understood in thyroid cancer. We 
      investigated the apoptotic effect of iodine on three different subtypes of 
      thyroid cancer cells. We observed that apoptosis induced by iodine was 
      mitochondrial-mediated. Iodine treatment decreased the level of mutant p53 
      including the R273H mutant that possesses anti-apoptotic features, but increased 
      the p21 level. Surprisingly, high doses of iodine promoted instead of suppressed 
      the expression of anti-apoptotic protein Bcl-xL expression. Moreover, iodine 
      transiently activated the subfamily members of mitogen activated protein kinases 
      (MAPKs) (ERK1/2, p38 and JNK1/2) which contribute to modulate p53, p21 and Bcl-xL 
      expression. The further results showed the three subfamily members of MAPKs all 
      worked as anti-apoptotic factors. Collectively, iodine-induced apoptotic pathway 
      is involved in the activation of MAPKs-related p21, Bcl-xL and mutant p53 
      regulation. The findings provide solid molecular evidence to explain the 
      potential pathway for iodine to influence thyroid cancer development. It may also 
      reveal some novel molecular targets for the treatment of thyroid cancer.
CI  - (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Liu, Xiao Hong
AU  - Liu XH
AD  - Department of Surgery, The Chinese University of Hong Kong, Prince of Wales 
      Hospital, Shatin, NT, Hong Kong, China.
FAU - Chen, George G
AU  - Chen GG
FAU - Vlantis, Alexander C
AU  - Vlantis AC
FAU - Tse, Gary M
AU  - Tse GM
FAU - van Hasselt, C Andrew
AU  - van Hasselt CA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100206
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (bcl-X Protein)
RN  - 9679TC07X4 (Iodine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Cyclin-Dependent Kinase Inhibitor p21/*metabolism
MH  - Cytoprotection/drug effects
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Iodine/*pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitochondria/drug effects/metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutation/genetics
MH  - Signal Transduction/drug effects
MH  - Thyroid Neoplasms/enzymology/*pathology
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Up-Regulation/drug effects
MH  - bcl-X Protein/*metabolism
EDAT- 2010/02/09 06:00
MHDA- 2010/06/09 06:00
CRDT- 2010/02/09 06:00
PHST- 2009/09/29 00:00 [received]
PHST- 2010/01/26 00:00 [revised]
PHST- 2010/02/02 00:00 [accepted]
PHST- 2010/02/09 06:00 [entrez]
PHST- 2010/02/09 06:00 [pubmed]
PHST- 2010/06/09 06:00 [medline]
AID - S0303-7207(10)00062-6 [pii]
AID - 10.1016/j.mce.2010.02.004 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2010 May 14;320(1-2):128-35. doi: 10.1016/j.mce.2010.02.004. 
      Epub 2010 Feb 6.