PMID- 29050265
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 41
DP  - 2017 Sep 19
TI  - Reactive oxygen species dependent phosphorylation of the liver kinase B1/AMP 
      activated protein kinase/ acetyl-CoA carboxylase signaling is critically involved 
      in apoptotic effect of lambertianic acid in hepatocellular carcinoma cells.
PG  - 70116-70129
LID - 10.18632/oncotarget.19592 [doi]
AB  - Though lambertianic acid (LA) is reported to have hypolipidemic activity in 
      liver, its underlying anticancer mechanism is poorly understood so far. Thus, in 
      the present study, apoptotic mechanism of LA was elucidated in HepG2 and SK-Hep1 
      hepatocellular carcinoma (HCC) cells. Here LA increased cytotoxicity, sub-G1 
      population and Annexin V/PI positive cells in two HCC cells. Also, LA cleaved 
      caspase-3 and poly(ADP-ribose) polymerase (PARP), activated phosphorylation of 
      liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK)/ acetyl-CoA 
      carboxylase (ACC) pathway and also suppressed antiapoptotic proteins such as 
      phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and the expression 
      of B cell lymphoma-2 (Bcl-2)/ B-cell lymphoma-extra large (Bcl-xL) and 
      cyclooxygenase-2 (COX-2) in two HCC cells. Furthermore, LA generated reactive 
      oxygen species (ROS) in HepG2 cells and AMPK inhibitor compound C or ROS 
      inhibitor N-acetyl-L-cysteine (NAC) blocked the apoptotic ability of LA to cleave 
      PARP or increase sub G1 population in HepG2 cells. Consistently, cleavages of 
      PARP and caspase-3 were induced by LA only in AMPK(+/+) MEF cells, but not in 
      AMPK(-/-) MEF cells. Also, immunoprecipitation (IP) revealed that phosphorylation 
      of LKB1/AMPK through their binding was enhanced in LA treated HepG2 cells. 
      Overall, these findings suggest that ROS dependent phosphorylation of 
      LKB1/AMPK/ACC signaling is critically involved in LA induced apoptosis in HCCs.
FAU - Jeong, Arong
AU  - Jeong A
AD  - Cancer Molecular Target Herbal Research Center, College of Korean Medicine, Kyung 
      Hee University, Seoul 131-701, Republic of Korea.
FAU - Kim, Ju-Ha
AU  - Kim JH
AD  - Cancer Molecular Target Herbal Research Center, College of Korean Medicine, Kyung 
      Hee University, Seoul 131-701, Republic of Korea.
FAU - Lee, Hyo-Jung
AU  - Lee HJ
AD  - Cancer Molecular Target Herbal Research Center, College of Korean Medicine, Kyung 
      Hee University, Seoul 131-701, Republic of Korea.
FAU - Kim, Sung-Hoon
AU  - Kim SH
AD  - Cancer Molecular Target Herbal Research Center, College of Korean Medicine, Kyung 
      Hee University, Seoul 131-701, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20170726
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5642540
OTO - NOTNLM
OT  - AMPK
OT  - ROS
OT  - apoptosis
OT  - hepatocellular carcinoma
OT  - lambertianic acid
COIS- CONFLICTS OF INTEREST The authors declare no competing financial interests.
EDAT- 2017/10/21 06:00
MHDA- 2017/10/21 06:01
PMCR- 2017/09/19
CRDT- 2017/10/21 06:00
PHST- 2017/02/09 00:00 [received]
PHST- 2017/06/20 00:00 [accepted]
PHST- 2017/10/21 06:00 [entrez]
PHST- 2017/10/21 06:00 [pubmed]
PHST- 2017/10/21 06:01 [medline]
PHST- 2017/09/19 00:00 [pmc-release]
AID - 19592 [pii]
AID - 10.18632/oncotarget.19592 [doi]
PST - epublish
SO  - Oncotarget. 2017 Jul 26;8(41):70116-70129. doi: 10.18632/oncotarget.19592. 
      eCollection 2017 Sep 19.