PMID- 30400136
OWN - NLM
STAT- MEDLINE
DCOM- 20190213
LR  - 20190215
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 10
IP  - 11
DP  - 2018 Nov 2
TI  - Docoxahexaenoic Acid Induces Apoptosis of Pancreatic Cancer Cells by Suppressing 
      Activation of STAT3 and NF-kappaB.
LID - 10.3390/nu10111621 [doi]
LID - 1621
AB  - The omega3-polyunsaturated fatty acid docosahexenoic acid (DHA) is known to induce 
      apoptosis of cancer cells. In this study, DHA was shown to reduce viability of 
      pancreatic cancer cells (PANC-1) by inducing DNA fragmentation, activating 
      caspase-3, and increasing the ratio of Bax/Bcl-2. To determine the DHA mechanism 
      of action, the impact of DHA on the activation of the key signaling proteins 
      epidermal growth factor receptor (EGFR), signal transducer and activator of 
      transcription factor 3 (STAT3), nuclear transcription factor-kappaB (NF-kappaB), and IkappaBalpha 
      in PANC-1 cells was probed. The observed DHA suppression of NF-kappaB DNA-binding 
      activity was found to result from reduced IkappaBalpha phosphorylation. The observed 
      DHA-induced suppression of STAT3 activation was found to be the result of 
      suppressed EGFR activation, which derives from the inhibitory effect of DHA on 
      the integrity of localization of EGFR to cell membrane lipid rafts. Since the 
      activation of STAT3 and NF-kappaB mediates the expression of survival genes cyclin D1 
      and survivin, DHA induced apoptosis by suppressing the STAT3/NF-kappaB-cyclin 
      D1/survivin axis. These results support the proposal that DHA-induced apoptosis 
      of pancreatic cells occurs via disruption of key pro-cell survival signaling 
      pathways. We suggest that the consumption of DHA-enriched foods could decrease 
      the incidence of pancreatic cancer.
FAU - Park, Mirae
AU  - Park M
AD  - Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human 
      Ecology, Yonsei University, Seoul 03722, Korea. mirae_0114@naver.com.
FAU - Lim, Joo Weon
AU  - Lim JW
AD  - Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human 
      Ecology, Yonsei University, Seoul 03722, Korea. jwlim11@yonsei.ac.kr.
FAU - Kim, Hyeyoung
AU  - Kim H
AUID- ORCID: 0000-0002-7019-917X
AD  - Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human 
      Ecology, Yonsei University, Seoul 03722, Korea. kim626@yonsei.ac.kr.
LA  - eng
GR  - Brain Korea 21 PLUS Project/Brain Korea 21 PLUS Project, College of Human 
      Ecology, Yonsei University/
PT  - Journal Article
DEP - 20181102
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (BIRC5 protein, human)
RN  - 0 (CCND1 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Survivin)
RN  - 136601-57-5 (Cyclin D1)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/*drug effects
MH  - Cyclin D1/genetics/metabolism
MH  - DNA Fragmentation
MH  - Docosahexaenoic Acids/administration & dosage/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - ErbB Receptors/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Membrane Microdomains/drug effects
MH  - NF-kappa B/metabolism
MH  - *Pancreatic Neoplasms
MH  - RNA, Messenger/genetics/metabolism
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - Survivin/genetics/metabolism
PMC - PMC6267441
OTO - NOTNLM
OT  - NF-kappaB
OT  - STAT3
OT  - apoptosis
OT  - docosahexaenoic acid
OT  - pancreatic cancer cells
COIS- The authors declare no conflict of interest.
EDAT- 2018/11/08 06:00
MHDA- 2019/02/14 06:00
PMCR- 2018/11/01
CRDT- 2018/11/08 06:00
PHST- 2018/10/10 00:00 [received]
PHST- 2018/10/22 00:00 [revised]
PHST- 2018/10/24 00:00 [accepted]
PHST- 2018/11/08 06:00 [entrez]
PHST- 2018/11/08 06:00 [pubmed]
PHST- 2019/02/14 06:00 [medline]
PHST- 2018/11/01 00:00 [pmc-release]
AID - nu10111621 [pii]
AID - nutrients-10-01621 [pii]
AID - 10.3390/nu10111621 [doi]
PST - epublish
SO  - Nutrients. 2018 Nov 2;10(11):1621. doi: 10.3390/nu10111621.