PMID- 31540489
OWN - NLM
STAT- MEDLINE
DCOM- 20200205
LR  - 20200205
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 24
IP  - 18
DP  - 2019 Sep 18
TI  - Proanthocyanidin-Rich Fractions from Red Rice Extract Enhance TNF-alpha-Induced Cell 
      Death and Suppress Invasion of Human Lung Adenocarcinoma Cell A549.
LID - 10.3390/molecules24183393 [doi]
LID - 3393
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a key role in promoting tumor 
      progression, such as stimulation of cell proliferation and metastasis via 
      activation of NF-kappaB and AP-1. The proanthocyanidin-rich fraction obtained from 
      red rice (PRFR) has been reported for its anti-tumor effects in cancer cells. 
      This study investigated the molecular mechanisms associated with PRFR on cell 
      survival and metastasis of TNF-alpha-induced A549 human lung adenocarcinoma. Notably, 
      PRFR enhanced TNF-alpha-induced A549 cell death when compared with PRFP alone and 
      caused a G0-G1 cell cycle arrest. Although, PRFR alone enhanced cell apoptosis, 
      the combination treatment induced the cells that had been enhanced with PRFR and 
      TNF-alpha to apoptosis that was less than PRFR alone and displayed a partial effect 
      on caspase-8 activation and PARP cleavage. By using the autophagy inhibitor; 3-MA 
      attenuated the effect of how PRFR enhanced TNF-alpha-induced cell death. This 
      indicates that PRFR not only enhanced TNF-alpha-induced A549 cell death by apoptotic 
      pathway, but also by induction autophagy. Moreover, PRFR also inhibited 
      TNF-alpha-induced A549 cell invasion. This effect was associated with PRFR suppressed 
      the TNF-alpha-induced level of expression for survival, proliferation, and invasive 
      proteins. This was due to reduce of MAPKs, Akt, NF-kappaB, and AP-1 activation. Taken 
      together, our results suggest that TNF-alpha-induced A549 cell survival and invasion 
      are attenuated by PRFR through the suppression of the MAPKs, Akt, AP-1, and NF-kappaB 
      signaling pathways.
FAU - Subkamkaew, Chayaporn
AU  - Subkamkaew C
AD  - Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang 
      Mai 50200, Thailand. subkamkaew@gmail.com.
FAU - Limtrakul Dejkriengkraikul, Pornngarm
AU  - Limtrakul Dejkriengkraikul P
AUID- ORCID: 0000-0003-4968-6667
AD  - Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang 
      Mai 50200, Thailand.
AD  - Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang 
      Mai University, Chiang Mai 50200, Thailand.
AD  - Center for Research and Development of Natural Products for Health, Chiang Mai 
      University, Chiang Mai 50200, Thailand.
FAU - Yodkeeree, Supachai
AU  - Yodkeeree S
AUID- ORCID: 0000-0001-9023-2283
AD  - Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang 
      Mai 50200, Thailand. yodkeelee@hotmail.com.
AD  - Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang 
      Mai University, Chiang Mai 50200, Thailand. yodkeelee@hotmail.com.
AD  - Center for Research and Development of Natural Products for Health, Chiang Mai 
      University, Chiang Mai 50200, Thailand. yodkeelee@hotmail.com.
LA  - eng
GR  - 096/2560/Faculty of Medicine, Chiang Mai University/
PT  - Journal Article
DEP - 20190918
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Plant Extracts)
RN  - 0 (Proanthocyanidins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 18206-61-6 (proanthocyanidin)
SB  - IM
MH  - A549 Cells
MH  - Adenocarcinoma of Lung/*metabolism/pathology
MH  - *Antineoplastic Agents, Phytogenic/chemistry/pharmacology
MH  - Autophagic Cell Death/*drug effects
MH  - Humans
MH  - Lung Neoplasms/*metabolism/pathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Neoplasm Invasiveness
MH  - Neoplasm Proteins/metabolism
MH  - Oryza/*chemistry
MH  - *Plant Extracts/chemistry/pharmacology
MH  - *Proanthocyanidins/chemistry/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC6767152
OTO - NOTNLM
OT  - TNF-alpha
OT  - autophagy
OT  - invasion
OT  - lung adenocarcinoma
OT  - proanthocyanins
COIS- The authors declare that they hold no conflicts of interest.
EDAT- 2019/09/22 06:00
MHDA- 2020/02/06 06:00
PMCR- 2019/09/18
CRDT- 2019/09/22 06:00
PHST- 2019/08/23 00:00 [received]
PHST- 2019/09/10 00:00 [revised]
PHST- 2019/09/17 00:00 [accepted]
PHST- 2019/09/22 06:00 [entrez]
PHST- 2019/09/22 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/09/18 00:00 [pmc-release]
AID - molecules24183393 [pii]
AID - molecules-24-03393 [pii]
AID - 10.3390/molecules24183393 [doi]
PST - epublish
SO  - Molecules. 2019 Sep 18;24(18):3393. doi: 10.3390/molecules24183393.