PMID- 32894559
OWN - NLM
STAT- MEDLINE
DCOM- 20210504
LR  - 20210504
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 24
IP  - 16
DP  - 2020 Aug
TI  - The role of GSTpi isoform in the cells signalling and anticancer therapy.
PG  - 8537-8550
LID - 22650 [pii]
LID - 10.26355/eurrev_202008_22650 [doi]
AB  - OBJECTIVE: The glutathione S-transferases (GSTs) overexpression in 
      hyperproliferating tumour cells resistant to chemotherapy was demonstrated. An 
      increased GST-pi activity weakens the efficacy of anti-cancer drugs by promoting 
      their efflux from cells. MATERIALS AND METHODS: This review summarises available 
      information on the physiological role of GSTs, in particular the role of GST-pi, 
      in regulation of signalling pathways mechanisms and cellular homeostasis for 
      understanding and explaining the basis for GST-pi application as a target for 
      anticancer therapy and implications for clinical practice. RESULTS: GST-pi can 
      weaken the effect of TNF receptor-associated factor 2 (TRAF2) on apoptosis 
      signal-regulating kinase-1 by inactivation of MAP kinase pathways (c-Jun 
      N-terminal, p38 kinases). GST-pi is involved in the metabolism of endogenous 
      lipids mediators, such as 15-detoxy-Delta12,14-prostaglandin J2 (15d-PGJ2). Reduced 
      binding of 15d-PGJ2 to peroxisome proliferator-activated receptors accompanied by 
      GST-pi can result in the inhibition of apoptosis. GSTP1 RNA is able to increase 
      the phosphorylation of signal transducer and activator of transcription 3, what 
      results in negative regulation as regards transcriptional activity thereof and 
      affects the growth factor signalling. However, the oxidation of GST-pi results in 
      inhibition of TRAF2-GST-pi complexes formation and unblocks cell apoptosis. The 
      inhibition of multidrug resistance related proteins 1 (MRP-1) promoter activity 
      and impairment of MRP-1 function can also act as a potent non-competitive 
      inhibitor of GST-pi. CONCLUSIONS: GST-pi is recognised as an important target in 
      designing new anticancer drugs. These drugs are often substrates for GST-pi or 
      have the affinity with its structure, what results in weakening its activity and 
      achieving therapeutic goal.
FAU - Sciskalska, M
AU  - Sciskalska M
AD  - Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw 
      Medical University, Wroclaw, Poland. milena.sciskalska@umed.wroc.pl.
FAU - Milnerowicz, H
AU  - Milnerowicz H
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Isoenzymes)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Glutathione Transferase/antagonists & inhibitors/chemistry/*metabolism
MH  - Humans
MH  - Isoenzymes/antagonists & inhibitors/chemistry/metabolism
MH  - Models, Molecular
MH  - Multidrug Resistance-Associated Proteins/antagonists & inhibitors/metabolism
MH  - Neoplasms/*drug therapy
MH  - Signal Transduction/drug effects
EDAT- 2020/09/08 06:00
MHDA- 2021/05/05 06:00
CRDT- 2020/09/07 12:13
PHST- 2020/09/07 12:13 [entrez]
PHST- 2020/09/08 06:00 [pubmed]
PHST- 2021/05/05 06:00 [medline]
AID - 22650 [pii]
AID - 10.26355/eurrev_202008_22650 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2020 Aug;24(16):8537-8550. doi: 
      10.26355/eurrev_202008_22650.