PMID- 29772714
OWN - NLM
STAT- MEDLINE
DCOM- 20180926
LR  - 20191210
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 5
DP  - 2018 May 16
TI  - Modulating Chemosensitivity of Tumors to Platinum-Based Antitumor Drugs by 
      Transcriptional Regulation of Copper Homeostasis.
LID - 10.3390/ijms19051486 [doi]
LID - 1486
AB  - Platinum (Pt)-based antitumor agents have been effective in treating many human 
      malignancies. Drug importing, intracellular shuffling, and exporting-carried out 
      by the high-affinity copper (Cu) transporter (hCtr1), Cu chaperone (Ato x1), and 
      Cu exporters (ATP7A and ATP7B), respectively-cumulatively contribute to the 
      chemosensitivity of Pt drugs including cisplatin and carboplatin, but not 
      oxaliplatin. This entire system can also handle Pt drugs via interactions between 
      Pt and the thiol-containing amino acid residues in these proteins; the 
      interactions are strongly influenced by cellular redox regulators such as 
      glutathione. hCtr1 expression is induced by acute Cu deprivation, and the 
      induction is regulated by the transcription factor specific protein 1 (Sp1) which 
      by itself is also regulated by Cu concentration variations. Copper displaces zinc 
      (Zn) coordination at the zinc finger (ZF) domains of Sp1 and inactivates its DNA 
      binding, whereas Cu deprivation enhances Sp1-DNA interactions and increases Sp1 
      expression, which in turn upregulates hCtr1. Because of the shared transport 
      system, chemosensitivity of Pt drugs can be modulated by targeting Cu 
      transporters. A Cu-lowering agent (trientine) in combination with a Pt drug 
      (carboplatin) has been used in clinical studies for overcoming Pt-resistance. 
      Future research should aim at further developing effective Pt drug retention 
      strategies for improving the treatment efficacy.
FAU - Lai, Yu-Hsuan
AU  - Lai YH
AD  - Department of Radiation Oncology, National Cheng Kung University Hospital, 
      College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan. 
      coscoscos.tw@hotmail.com.
AD  - Institute of Clinical Medicine, College of Medicine, National Cheng Kung 
      University, Tainan 70428, Taiwan. coscoscos.tw@hotmail.com.
FAU - Kuo, Chin
AU  - Kuo C
AD  - Department of Radiation Oncology, National Cheng Kung University Hospital, 
      College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan. 
      tiffa663@gmail.com.
FAU - Kuo, Macus Tien
AU  - Kuo MT
AD  - Department of Translational Molecular Pathology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77054, USA. tienkuo@sbcglobal.net.
FAU - Chen, Helen H W
AU  - Chen HHW
AD  - Department of Radiation Oncology, National Cheng Kung University Hospital, 
      College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan. 
      helen@mail.ncku.edu.tw.
AD  - Center of Applied Nanomedicine, National Cheng Kung University, Tainan 70101, 
      Taiwan. helen@mail.ncku.edu.tw.
LA  - eng
GR  - R01 CA149260/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20180516
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Copper Transporter 1)
RN  - 0 (SLC31A1 protein, human)
RN  - 49DFR088MY (Platinum)
RN  - 789U1901C5 (Copper)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Cation Transport Proteins/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cisplatin/pharmacology
MH  - Copper/*metabolism
MH  - Copper Transporter 1
MH  - Drug Resistance, Neoplasm
MH  - Gene Expression Regulation, Neoplastic
MH  - *Homeostasis
MH  - Humans
MH  - Oxidation-Reduction
MH  - Platinum/*pharmacology
MH  - *Transcription, Genetic
PMC - PMC5983780
OTO - NOTNLM
OT  - Sp1
OT  - cisplatin
OT  - drug-resistance
OT  - hCtr1
OT  - high-affinity copper transporter
OT  - ovarian cancers
COIS- The authors declare no conflict of interest.
EDAT- 2018/05/19 06:00
MHDA- 2018/09/27 06:00
PMCR- 2018/05/01
CRDT- 2018/05/19 06:00
PHST- 2018/04/23 00:00 [received]
PHST- 2018/05/10 00:00 [revised]
PHST- 2018/05/12 00:00 [accepted]
PHST- 2018/05/19 06:00 [entrez]
PHST- 2018/05/19 06:00 [pubmed]
PHST- 2018/09/27 06:00 [medline]
PHST- 2018/05/01 00:00 [pmc-release]
AID - ijms19051486 [pii]
AID - ijms-19-01486 [pii]
AID - 10.3390/ijms19051486 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 May 16;19(5):1486. doi: 10.3390/ijms19051486.