PMID- 31671847
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 11
IP  - 11
DP  - 2019 Oct 29
TI  - NEDD9 Inhibition by miR-25-5p Activation Is Critically Involved in Co-Treatment 
      of Melatonin- and Pterostilbene-Induced Apoptosis in Colorectal Cancer Cells.
LID - 10.3390/cancers11111684 [doi]
LID - 1684
AB  - The underlying interaction between melatonin (MLT) and daily fruit intake still 
      remains unclear to date, despite multibiological effects of MLT. Herein, the 
      apoptotic mechanism by co-treatment of MLT and pterostilbene (Ptero) contained 
      mainly in grape and blueberries was elucidated in colorectal cancers (CRCs). MLT 
      and Ptero co-treatment (MLT+Ptero) showed synergistic cytotoxicity compared with 
      MLT or Ptero alone, reduced the number of colonies and Ki67 expression, and also 
      increased terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL) 
      positive cells and reactive oxygen species (ROS) production in CRCs. 
      Consistently, MLT+Ptero cleaved caspase 3 and poly (ADP-ribose) polymerase 
      (PARP), activated sex-determining region Y-Box10 (SOX10), and also attenuated the 
      expression of Bcl-xL, neural precursor cell expressed developmentally 
      downregulated protein 9 (NEDD9), and SOX9 in CRCs. Additionally, MLT+Ptero 
      induced differentially expressed microRNAs (upregulation: miR-25-5p, miR-542-5p, 
      miR-711, miR-4725-3p, and miR-4484; downregulation: miR-4504, miR-668-3p, 
      miR-3121-5p, miR-195-3p, and miR-5194) in HT29 cells. Consistently, MLT +Ptero 
      upregulated miR-25-5p at mRNA level and conversely NEDD9 overexpression or 
      miR-25-5p inhibitor reversed the ability of MLT+Ptero to increase cytotoxicity, 
      suppress colony formation, and cleave PARP in CRCs. Furthermore, 
      immunofluorescence confirmed miR-25-5p inhibitor reversed the reduced 
      fluorescence of NEDD9 and increased SOX10 by MLT+Ptero in HT29 cells. Taken 
      together, our findings provided evidence that MLT+Ptero enhances apoptosis via 
      miR-25-5p mediated NEDD9 inhibition in colon cancer cells as a potent strategy 
      for colorectal cancer therapy.
FAU - Jung, Ji Hoon
AU  - Jung JH
AUID- ORCID: 0000-0002-5644-5960
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. johnsperfume@gmail.com.
FAU - Shin, Eun Ah
AU  - Shin EA
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. eunah1008@khu.ac.kr.
FAU - Kim, Ju-Ha
AU  - Kim JH
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. 964juha@daum.net.
FAU - Sim, Deok Yong
AU  - Sim DY
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. simdy0821@naver.com.
FAU - Lee, Hyemin
AU  - Lee H
AUID- ORCID: 0000-0003-3910-5611
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. glansy555@gmail.com.
FAU - Park, Ji Eon
AU  - Park JE
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. wdnk77@naver.com.
FAU - Lee, Hyo-Jung
AU  - Lee HJ
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. hyonice77@naver.com.
FAU - Kim, Sung-Hoon
AU  - Kim SH
AUID- ORCID: 0000-0003-2423-1973
AD  - Cancer Molecular Targeted Herbal Research Laboratory, College of Kyung Hee 
      Medicine, Kyung Hee University, Seoul 02447, Korea. sungkim7@khu.ac.kr.
LA  - eng
GR  - 2017R1A2A1A17069297/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20191029
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6895813
OTO - NOTNLM
OT  - MLT
OT  - NEDD9
OT  - Ptero
OT  - apoptosis
OT  - miR-25-5p
OT  - synergy
COIS- The authors declare no conflict of interest.
EDAT- 2019/11/02 06:00
MHDA- 2019/11/02 06:01
PMCR- 2019/10/29
CRDT- 2019/11/02 06:00
PHST- 2019/09/30 00:00 [received]
PHST- 2019/10/16 00:00 [revised]
PHST- 2019/10/23 00:00 [accepted]
PHST- 2019/11/02 06:00 [entrez]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2019/11/02 06:01 [medline]
PHST- 2019/10/29 00:00 [pmc-release]
AID - cancers11111684 [pii]
AID - cancers-11-01684 [pii]
AID - 10.3390/cancers11111684 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 Oct 29;11(11):1684. doi: 10.3390/cancers11111684.