PMID- 26201693
OWN - NLM
STAT- MEDLINE
DCOM- 20160517
LR  - 20220330
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 47
IP  - 3
DP  - 2015 Sep
TI  - Naringin induces autophagy-mediated growth inhibition by downregulating the 
      PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells.
PG  - 1061-9
LID - 10.3892/ijo.2015.3095 [doi]
AB  - Naringin, one of the major bioflavonoid of Citrus, has been demonstrated as 
      potential anticancer agent. However, the underlying anticancer mechanism still 
      needs to be explored further. This study investigated the inhibitory effect of 
      Naringin on human AGS cancer cells. AGS cell proliferation was inhibited by 
      Naringin in a dose- and time-dependent manner. Naringin did not induce apoptotic 
      cell death, determined by no DNA fragmentation and the reduced Bax/Bcl-xL ratio. 
      Growth inhibitory role of Naringin was observed by western blot analysis 
      demonstrating downregulation of PI3K/Akt/mTOR cascade with an upregulated 
      p21CIPI/WAFI. Formation of cytoplasmic vacuoles and autophagosomes were observed 
      in Naringin-treated AGS cells, further confirmed by the activation of autophagic 
      proteins Beclin 1 and LC3B with a significant phosphorylation of mitogen 
      activated protein kinases (MAPKs). Collectively, our observed results determined 
      that anti-proliferative activity of Naringin in AGS cancer cells is due to 
      suppression of PI3K/Akt/mTOR cascade via induction of autophagy with activated 
      MAPKs. Thus, the present finding suggests that Naringin induced autophagy- 
      mediated growth inhibition shows potential as an alternative therapeutic agent 
      for human gastric carcinoma.
FAU - Raha, Suchismita
AU  - Raha S
AD  - Research Institute of Life Science and College of Veterinary Medicine (BK21 plus 
      project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of 
      Korea.
FAU - Yumnam, Silvia
AU  - Yumnam S
AD  - Research Institute of Life Science and College of Veterinary Medicine (BK21 plus 
      project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of 
      Korea.
FAU - Hong, Gyeong Eun
AU  - Hong GE
AD  - Research Institute of Life Science and College of Veterinary Medicine (BK21 plus 
      project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of 
      Korea.
FAU - Lee, Ho Jeong
AU  - Lee HJ
AD  - Research Institute of Life Science and College of Veterinary Medicine (BK21 plus 
      project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of 
      Korea.
FAU - Saralamma, Venu Venkatarame Gowda
AU  - Saralamma VV
AD  - Research Institute of Life Science and College of Veterinary Medicine (BK21 plus 
      project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of 
      Korea.
FAU - Park, Hyeon-Soo
AU  - Park HS
AD  - Research Institute of Life Science and College of Veterinary Medicine (BK21 plus 
      project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of 
      Korea.
FAU - Heo, Jeong Doo
AU  - Heo JD
AD  - Gyeongnam Department of Environmental Toxicology and Chemistry, Toxicology 
      Screening Research Center, Korea Institute of Toxicology, Jinju 666-844, Republic 
      of Korea.
FAU - Lee, Sang Joon
AU  - Lee SJ
AD  - Gyeongnam Department of Environmental Toxicology and Chemistry, Toxicology 
      Screening Research Center, Korea Institute of Toxicology, Jinju 666-844, Republic 
      of Korea.
FAU - Kim, Eun Hee
AU  - Kim EH
AD  - Department of Nursing Science, International University of Korea, Moonsan, Jinju 
      660-759, Republic of Korea.
FAU - Kim, Jin-A
AU  - Kim JA
AD  - Department of Physical Therapy, International University of Korea, Moonsan, Jinju 
      660-759, Republic of Korea.
FAU - Kim, Gon Sup
AU  - Kim GS
AD  - Research Institute of Life Science and College of Veterinary Medicine (BK21 plus 
      project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150720
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Flavanones)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - N7TD9J649B (naringin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Autophagy
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Flavanones/*pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/*drug effects
MH  - Stomach Neoplasms/drug therapy/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2015/07/24 06:00
MHDA- 2016/05/18 06:00
CRDT- 2015/07/24 06:00
PHST- 2015/06/03 00:00 [received]
PHST- 2015/06/26 00:00 [accepted]
PHST- 2015/07/24 06:00 [entrez]
PHST- 2015/07/24 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
AID - 10.3892/ijo.2015.3095 [doi]
PST - ppublish
SO  - Int J Oncol. 2015 Sep;47(3):1061-9. doi: 10.3892/ijo.2015.3095. Epub 2015 Jul 20.