PMID- 26572581
OWN - NLM
STAT- MEDLINE
DCOM- 20161014
LR  - 20161230
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 37
IP  - 1
DP  - 2016 Jan
TI  - Orexin A induces autophagy in HCT-116 human colon cancer cells through the ERK 
      signaling pathway.
PG  - 126-32
LID - 10.3892/ijmm.2015.2409 [doi]
AB  - Orexins are a class of peptides which have a potent influence on a broad variety 
      of cancer cells. Autophagy is closely associated with tumors; however, its 
      function is not yet completely understood. In this study, we aimed to determine 
      whether orexin A induces autophagy in HCT‑116 human colon cancer cells and to 
      elucidate the molecular mechanisms involved. For this purpose, HCT‑116 cells were 
      treated with orexin A, and cell viability was then measured by MTT assay, and 
      apoptosis was determined by flow cytometry. The expression levels of 
      autophagy‑related proteins were measured by western blot analysis. Quantitative 
      analysis of autophagy following acridine orange (AO) staining was performed using 
      fluorescence microscopy, and cellular morphology was observed under a 
      transmission electron microscope. In addition, the HCT‑116 cells were treated 
      with the extracellular signal‑regulated kinase (ERK) inhibitor, U0126, or the 
      autophagy inhibitor, chloroquine, in combination with orexin A in order to 
      examine the activation of ERK. We found that orexin A significantly inhibited the 
      viability of the HCT‑116 cells. Both autophagy and apoptosis were activated 
      during the orexin A‑induced death of HCT‑116 cells. When the HCT‑116 cells were 
      treated with orexin A for 24 h, an accumulation of punctate 
      microtubule-associated protein-1 light chain 3 (LC3) and an increase in LC3‑Ⅱ 
      protein levels were also detected, indicating the activation of autophagy. 
      Moreover, orexin A upregulated ERK phosphorylation; however, U0126 or chloroquine 
      abrogated ERK phosphorylation and decreased autophagy, compared to treatment with 
      orexin A alone. Therefore, our findings demonstratedm that orexin A induced 
      autophagy through the ERK pathway in HCT‑116 human colon cancer cells. The 
      inhibition of autophagy may thus prove to be an effective strategy for enhancing 
      the antitumor potential of orexin A as a treatment for colon cancer.
FAU - Wen, Jing
AU  - Wen J
AD  - Department of Endocrinology, First Affiliated Hospital, China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
FAU - Zhao, Yuyan
AU  - Zhao Y
AD  - Department of Endocrinology, First Affiliated Hospital, China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
FAU - Guo, Lei
AU  - Guo L
AD  - Department of Orthopedic Surgery, First Affiliated Hospital, China Medical 
      University, Shenyang, Liaoning 110001, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151113
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Orexins)
SB  - IM
MH  - Apoptosis
MH  - *Autophagy
MH  - Cell Survival
MH  - Colon/metabolism/*pathology
MH  - Colonic Neoplasms/*metabolism/*pathology
MH  - HCT116 Cells
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - Orexins/*metabolism
EDAT- 2015/11/18 06:00
MHDA- 2016/10/16 06:00
CRDT- 2015/11/18 06:00
PHST- 2015/03/14 00:00 [received]
PHST- 2015/10/07 00:00 [accepted]
PHST- 2015/11/18 06:00 [entrez]
PHST- 2015/11/18 06:00 [pubmed]
PHST- 2016/10/16 06:00 [medline]
AID - 10.3892/ijmm.2015.2409 [doi]
PST - ppublish
SO  - Int J Mol Med. 2016 Jan;37(1):126-32. doi: 10.3892/ijmm.2015.2409. Epub 2015 Nov 
      13.