PMID- 32755671
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20210527
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 160
DP  - 2020 Nov 20
TI  - Gamma irradiation promotes chemo-sensitization potential of gallic acid through 
      attenuation of autophagic flux to trigger apoptosis in an NRF2 inactivation 
      signalling pathway.
PG  - 111-124
LID - S0891-5849(20)31119-9 [pii]
LID - 10.1016/j.freeradbiomed.2020.06.022 [doi]
AB  - Ionizing radiation has the potential to cause structural modification or change 
      in electrochemical properties in parent lead pharmacophores that exhibit enhanced 
      bioactivity. Gallic acid (GA), a triphenolic compound has displayed potent 
      anticancer drug potency due to its withstanding antioxidant propensity. This 
      study uncovered the comparative efficacy of gamma-irradiated gallic acid (GAIR) 
      in the modulation of an antioxidant system for regulation apoptosis and 
      autophagy. GAIR exhibited remarkable anti-proliferative efficacy as shown by MTT, 
      clonogenic survival, and scratch assay. In addition to this, GAIR promoted 
      intrinsic apoptosis through mitochondrial superoxide generation. GAIR decreased 
      the activity of antioxidant enzymes by downregulating nuclear factor erythroid 
      2-related factor 2 (NRF2) and its downstream effector molecules NAD(P)H Quinone 
      Dehydrogenase 1 (NQO1) and gamma-glutamylcysteine synthetase (GCLC). 
      Simultaneously, GAIR attenuated autophagosome-lysosome fusion without altering 
      the lysosomal activity. Inhibition of autophagic flux resulted in the 
      accumulation of lipid droplets (LDs) such as hexadecanoic acid and oleic acid 
      that fuelled superoxide generation leading to apoptosis. In the meantime, under 
      oxidative upset, conversion of LDs to free fatty acids reduced leading to 
      inhibition of ATP generation that subsequently provoked apoptosis. The effects of 
      autophagy inhibition by GAIR on the therapeutic efficacy of chemotherapeutic 
      drugs was studied and the co-treatment markedly decreased the cell viability and 
      increased apoptosis. Further, GAIR exhibited potent antitumor activity in 
      Dalton's Lymphoma-tumor bearing mice through modulation of apoptosis and 
      autophagy without toxic activity. In conclusion, change in electrochemical 
      properties by gamma radiation enhances the anticancer efficacy of gallic acid 
      through superoxide mediated apoptosis fuelled by inhibition of lipophagy in an 
      NRF2 dependent signaling pathway.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Patra, Srimanta
AU  - Patra S
AD  - Cancer and Cell Death Laboratory, Department of Life Science, National Institute 
      of Technology Rourkela, India.
FAU - Bhol, Chandra Sekhar
AU  - Bhol CS
AD  - Cancer and Cell Death Laboratory, Department of Life Science, National Institute 
      of Technology Rourkela, India.
FAU - Panigrahi, Debasna Pritimanjari
AU  - Panigrahi DP
AD  - Cancer and Cell Death Laboratory, Department of Life Science, National Institute 
      of Technology Rourkela, India.
FAU - Praharaj, Prakash Priyadarshi
AU  - Praharaj PP
AD  - Cancer and Cell Death Laboratory, Department of Life Science, National Institute 
      of Technology Rourkela, India.
FAU - Pradhan, Biswajita
AU  - Pradhan B
AD  - PG Department of Botany, Berhampur University, Berhampur, 760007, India.
FAU - Jena, Mrutyunjay
AU  - Jena M
AD  - PG Department of Botany, Berhampur University, Berhampur, 760007, India.
FAU - Bhutia, Sujit Kumar
AU  - Bhutia SK
AD  - Cancer and Cell Death Laboratory, Department of Life Science, National Institute 
      of Technology Rourkela, India. Electronic address: sujitb@nitrkl.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200802
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Reactive Oxygen Species)
RN  - 632XD903SP (Gallic Acid)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - *Autophagy
MH  - *Gallic Acid/pharmacology
MH  - Mice
MH  - *NF-E2-Related Factor 2/genetics/metabolism
MH  - Reactive Oxygen Species
MH  - Signal Transduction
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Gallic acid
OT  - Gamma-irradiation
OT  - Superoxide
EDAT- 2020/08/07 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/08/07 06:00
PHST- 2020/03/06 00:00 [received]
PHST- 2020/05/25 00:00 [revised]
PHST- 2020/06/08 00:00 [accepted]
PHST- 2020/08/07 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/08/07 06:00 [entrez]
AID - S0891-5849(20)31119-9 [pii]
AID - 10.1016/j.freeradbiomed.2020.06.022 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2020 Nov 20;160:111-124. doi: 
      10.1016/j.freeradbiomed.2020.06.022. Epub 2020 Aug 2.