PMID- 27263528
OWN - NLM
STAT- MEDLINE
DCOM- 20180502
LR  - 20220317
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jun 6
TI  - Docetaxel induced-JNK2/PHD1 signaling pathway increases degradation of HIF-1alpha and 
      causes cancer cell death under hypoxia.
PG  - 27382
LID - 10.1038/srep27382 [doi]
LID - 27382
AB  - HIF-1 (hypoxia-inducible factor-1) regulates the expression of more than 70 genes 
      involved in angiogenesis, tumor growth, metastasis, chemoresistance, and 
      radioresistance. Thus, there is growing interest in using HIF-1 inhibitors as 
      anticancer drugs. Docetaxel, a Food and Drug Administration-approved anticancer 
      drug, is reported to enhance HIF-1alpha degradation. Here, we investigated the 
      molecular mechanism underlying docetaxel-induced HIF-1alpha degradation and cancer 
      cell death under hypoxic conditions. Docetaxel pretreatment enhanced the 
      polyubiquitination and proteasome-mediated degradation of HIF-1alpha, and increased 
      cancer cell death under hypoxic conditions. Docetaxel also activated the prolyl 
      hydroxylase, PHD1, in hypoxia, and pharmacological inhibition or siRNA-mediated 
      knockdown of PHD1 prevented docetaxel-induced HIF-1alpha degradation and cancer cell 
      death. Additionally, siRNA-mediated JNK2 knockdown blocked docetaxel-induced 
      HIF-1alpha degradation and cancer cell death by inhibiting PHD1 activation. A 
      luciferase reporter assay revealed that inhibition of the JNK2/PHD1 signaling 
      pathway significantly increased the transcriptional activity of HIF-1 in 
      docetaxel-treated cancer cells under hypoxia. Consistent with these results, 
      docetaxel-treated JNK2-knockdown tumors grew much faster than control tumors 
      through inhibition of docetaxel-induced PHD1 activation and degradation of 
      HIF-1alpha. Our results collectively show that, under hypoxic conditions, docetaxel 
      induces apoptotic cell death through JNK2/PHD1 signaling-mediated HIF-1alpha 
      degradation.
FAU - Oh, Eun-Taex
AU  - Oh ET
AD  - Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 
      22212, Republic of Korea.
AD  - Hypoxia-related Disease Research Center, College of Medicine, Inha University, 
      Incheon 22212, Republic of Korea.
FAU - Kim, Chan Woo
AU  - Kim CW
AD  - Department of Microbiology, College of Medicine, Inha University, Incheon 22212, 
      Republic of Korea.
FAU - Kim, Soo Jung
AU  - Kim SJ
AD  - Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 
      22212, Republic of Korea.
FAU - Lee, Jae-Seon
AU  - Lee JS
AD  - Hypoxia-related Disease Research Center, College of Medicine, Inha University, 
      Incheon 22212, Republic of Korea.
AD  - Department of Molecular Medicine, College of Medicine, Inha University, Incheon 
      22212, Republic of Korea.
FAU - Hong, Soon-Sun
AU  - Hong SS
AD  - Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 
      22212, Republic of Korea.
AD  - Hypoxia-related Disease Research Center, College of Medicine, Inha University, 
      Incheon 22212, Republic of Korea.
FAU - Park, Heon Joo
AU  - Park HJ
AD  - Hypoxia-related Disease Research Center, College of Medicine, Inha University, 
      Incheon 22212, Republic of Korea.
AD  - Department of Microbiology, College of Medicine, Inha University, Incheon 22212, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160606
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - EC 1.14.11.29 (EGLN2 protein, human)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Cell Death/*drug effects
MH  - *Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Docetaxel
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases/chemistry/*metabolism
MH  - Mitogen-Activated Protein Kinase 9/genetics/*metabolism
MH  - Neoplasms/enzymology/metabolism/*pathology
MH  - Proteolysis
MH  - Signal Transduction/*drug effects
MH  - Taxoids/*pharmacology
MH  - Ubiquitination
PMC - PMC4893693
EDAT- 2016/06/07 06:00
MHDA- 2018/05/03 06:00
PMCR- 2016/06/06
CRDT- 2016/06/07 06:00
PHST- 2016/01/27 00:00 [received]
PHST- 2016/05/18 00:00 [accepted]
PHST- 2016/06/07 06:00 [entrez]
PHST- 2016/06/07 06:00 [pubmed]
PHST- 2018/05/03 06:00 [medline]
PHST- 2016/06/06 00:00 [pmc-release]
AID - srep27382 [pii]
AID - 10.1038/srep27382 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jun 6;6:27382. doi: 10.1038/srep27382.