PMID- 26729093
OWN - NLM
STAT- MEDLINE
DCOM- 20161025
LR  - 20220409
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 17
IP  - 1
DP  - 2015 Dec 29
TI  - Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in 
      HT29 and Caco-2 Cells.
LID - 10.3390/ijms17010041 [doi]
LID - 41
AB  - Colorectal cancer (CRC) is one of the most common malignancies worldwide with 
      substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase 
      A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This 
      study aimed to evaluate the molecular interactome and anticancer effect of ALS 
      and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly 
      arrested cells in G(2)/M phase in both cell lines, accompanied by remarkable 
      alterations in the expression level of key cell cycle regulators. ALS induced 
      apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor 
      pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the 
      suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian 
      target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase 
      (AMPK) signaling pathways. There was a differential modulating effect of ALS on 
      p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition 
      of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS 
      potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 
      cells. Collectively, it suggests that induction of cell cycle arrest, promotion 
      of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death 
      receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the 
      cancer cell killing effect of ALS on CRC cells.
FAU - Ren, Bao-Jun
AU  - Ren BJ
AD  - Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated 
      to Southern Medical University, Guangdong 528300, China. rbjsdyy@outlook.com.
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612, USA. 
      rbjsdyy@outlook.com.
FAU - Zhou, Zhi-Wei
AU  - Zhou ZW
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612, USA. 
      zzhou1@health.usf.edu.
FAU - Zhu, Da-Jian
AU  - Zhu DJ
AD  - Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated 
      to Southern Medical University, Guangdong 528300, China. zdjsdyy@outlook.com.
FAU - Ju, Yong-Le
AU  - Ju YL
AD  - Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated 
      to Southern Medical University, Guangdong 528300, China. jylsdyy@outlook.com.
FAU - Wu, Jin-Hao
AU  - Wu JH
AD  - Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated 
      to Southern Medical University, Guangdong 528300, China. wjhsdyy@outlook.com.
FAU - Ouyang, Man-Zhao
AU  - Ouyang MZ
AD  - Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated 
      to Southern Medical University, Guangdong 528300, China. oymzsdyy@outlook.com.
FAU - Chen, Xiao-Wu
AU  - Chen XW
AD  - Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated 
      to Southern Medical University, Guangdong 528300, China. cxwsdyy@outlook.com.
FAU - Zhou, Shu-Feng
AU  - Zhou SF
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612, USA. 
      szhou@health.usf.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151229
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Azepines)
RN  - 0 (MLN 8237)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adenocarcinoma/enzymology/*metabolism
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Azepines/*pharmacology
MH  - Caco-2 Cells
MH  - Cell Cycle Checkpoints/*drug effects
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - HT29 Cells
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyrimidines/*pharmacology
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC4730286
OTO - NOTNLM
OT  - EMT
OT  - alisertib
OT  - cell cycle
OT  - colorectal cancer
OT  - programmed cell death
EDAT- 2016/01/06 06:00
MHDA- 2016/10/26 06:00
PMCR- 2016/01/01
CRDT- 2016/01/06 06:00
PHST- 2015/11/02 00:00 [received]
PHST- 2015/12/07 00:00 [revised]
PHST- 2015/12/09 00:00 [accepted]
PHST- 2016/01/06 06:00 [entrez]
PHST- 2016/01/06 06:00 [pubmed]
PHST- 2016/10/26 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - ijms17010041 [pii]
AID - ijms-17-00041 [pii]
AID - 10.3390/ijms17010041 [doi]
PST - epublish
SO  - Int J Mol Sci. 2015 Dec 29;17(1):41. doi: 10.3390/ijms17010041.