PMID- 29247770
OWN - NLM
STAT- MEDLINE
DCOM- 20180507
LR  - 20180507
IS  - 1873-6351 (Electronic)
IS  - 0278-6915 (Linking)
VI  - 111
DP  - 2018 Jan
TI  - Apigenin promotes TRAIL-mediated apoptosis regardless of ROS generation.
PG  - 623-630
LID - S0278-6915(17)30759-7 [pii]
LID - 10.1016/j.fct.2017.12.018 [doi]
AB  - Apigenin is a bioactive flavone in several herbs including parsley, thyme, and 
      peppermint. Apigenin possesses anti-cancer and anti-inflammatory properties; 
      however, whether apigenin enhances TRAIL-mediated apoptosis in cancer cells is 
      unknown. In the current study, we found that apigenin enhanced TRAIL-induced 
      apoptosis by promoting caspase activation and death receptor 5 (DR5) expression 
      and a chimeric antibody against DR5 completely blocked the apoptosis. Apigenin 
      also upregulated reactive oxygen species (ROS) generation; however, intriguingly, 
      ROS inhibitors, glutathione (GSH) or N-acetyl-l-cysteine (NAC), moderately 
      increased apigenin/TRAIL-induced apoptosis. Additional results showed that an 
      autophagy inducer, rapamycin, enhanced apigenin/TRAIL-mediated apoptosis by a 
      slight increase of ROS generation. Accordingly, NAC and GSH rather decreased 
      apigenin-induced autophagy formation, suggesting that apigenin-induced ROS 
      generation increased autophagy formation. However, autophagy inhibitors, 
      bafilomycin (BAF) and 3-methyladenine (3-MA), showed different result in 
      apigenin/TRAIL-mediated apoptosis without ROS generation. 3-MA upregulated the 
      apoptosis but remained ROS levels; however, no changes on apoptosis and ROS 
      generation were observed by BAF treatment. Taken together, these findings reveal 
      that apigenin enhances TRAIL-induced apoptosis by activating apoptotic caspases 
      by upregulating DR5 expression regardless of ROS generation, which may be a 
      promising strategy for an adjuvant of TRAIL.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Kang, Chang-Hee
AU  - Kang CH
AD  - Department of Marine Life Sciences, Jeju National University, Jeju 63243, 
      Republic of Korea; Freshwater Bioresources Utilization Bureau, Bioresources 
      Industrialization Research Division, Sangju-si, Gyeongsangbuk-do 37242, Republic 
      of Korea.
FAU - Molagoda, Ilandarage Menu Neelaka
AU  - Molagoda IMN
AD  - Department of Marine Life Sciences, Jeju National University, Jeju 63243, 
      Republic of Korea.
FAU - Choi, Yung Hyun
AU  - Choi YH
AD  - Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, 
      Busan 47340, Republic of Korea.
FAU - Park, Cheol
AU  - Park C
AD  - Department of Molecular Biology, College of Natural Sciences and Human Ecology, 
      Dong-Eui University, Busan 47340, Republic of Korea.
FAU - Moon, Dong-Oh
AU  - Moon DO
AD  - Department of Biology Education, Daegu University, Gyeongsan, Gyeongbuk 38453, 
      Republic of Korea.
FAU - Kim, Gi-Young
AU  - Kim GY
AD  - Department of Marine Life Sciences, Jeju National University, Jeju 63243, 
      Republic of Korea. Electronic address: immunkim@jejunu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20171213
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 7V515PI7F6 (Apigenin)
SB  - IM
MH  - Apigenin/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/drug effects
MH  - Cell Line, Tumor
MH  - Humans
MH  - Reactive Oxygen Species/*metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/*metabolism
OTO - NOTNLM
OT  - Apigenin
OT  - Autophagy
OT  - Reactive oxygen species
OT  - Tumor necrosis factor-related apoptosis-inducing ligand
EDAT- 2017/12/17 06:00
MHDA- 2018/05/08 06:00
CRDT- 2017/12/17 06:00
PHST- 2017/03/03 00:00 [received]
PHST- 2017/12/08 00:00 [revised]
PHST- 2017/12/12 00:00 [accepted]
PHST- 2017/12/17 06:00 [pubmed]
PHST- 2018/05/08 06:00 [medline]
PHST- 2017/12/17 06:00 [entrez]
AID - S0278-6915(17)30759-7 [pii]
AID - 10.1016/j.fct.2017.12.018 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2018 Jan;111:623-630. doi: 10.1016/j.fct.2017.12.018. Epub 
      2017 Dec 13.