PMID- 20642839
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20220409
IS  - 1750-2187 (Electronic)
IS  - 1750-2187 (Linking)
VI  - 5
DP  - 2010 Jul 19
TI  - Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO 
      transcription factor, leading to cell cycle arrest and apoptosis in pancreatic 
      cancer.
PG  - 10
LID - 10.1186/1750-2187-5-10 [doi]
AB  - BACKGROUND: Mammalian forkhead members of the class O (FOXO) transcription 
      factors, including FOXO1, FOXO3a, and FOXO4, are implicated in the regulation of 
      several biological processes, including the stress resistance, metabolism, cell 
      cycle, apoptosis and DNA repair. The objectives of this study were to examine the 
      molecular mechanisms by which FOXO transcription factors induced cell cycle 
      arrest and apoptosis and enhanced anti-proliferative effects of sulforaphane 
      (SFN, an active compound in cruciferous vegetables) in pancreatic cancer cells. 
      RESULTS: Our data demonstrated that SFN inhibited cell proliferation and colony 
      formation, and induced apoptosis through caspase-3 activation in pancreatic 
      cancer cells. The inhibition of PI3K/AKT and MEK/ERK pathways activated FOXO 
      transcription factors. SFN inhibited phosphorylation of AKT and ERK, and 
      activated FOXO transcription factors, leading to cell cycle arrest and apoptosis. 
      Phosphorylation deficient mutants of FOXO proteins enhanced FOXO transcriptional 
      activity, and further enhanced SFN-induced FOXO activity and apoptosis. SFN 
      induced the expression of p21/CIP1 and p27/KIP1, and inhibited the expression of 
      cyclin D1. CONCLUSION: These data suggest that inhibition of PI3K/AKT and ERK 
      pathways acts together to activate FOXO transcription factor and enhances 
      SFN-induced FOXO transcriptional activity, leading to cell cycle arrest and 
      apoptosis.
FAU - Roy, Sanjit K
AU  - Roy SK
AD  - Department of Pathology and Laboratory Medicine, The University of Kansas Cancer 
      Center, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas 
      City, KS, 66160, USA. sshankar@kumc.edu.
FAU - Srivastava, Rakesh K
AU  - Srivastava RK
FAU - Shankar, Sharmila
AU  - Shankar S
LA  - eng
PT  - Journal Article
DEP - 20100719
PL  - England
TA  - J Mol Signal
JT  - Journal of molecular signaling
JID - 101271526
PMC - PMC2915986
EDAT- 2010/07/21 06:00
MHDA- 2010/07/21 06:01
PMCR- 2010/07/19
CRDT- 2010/07/21 06:00
PHST- 2010/06/22 00:00 [received]
PHST- 2010/07/19 00:00 [accepted]
PHST- 2010/07/21 06:00 [entrez]
PHST- 2010/07/21 06:00 [pubmed]
PHST- 2010/07/21 06:01 [medline]
PHST- 2010/07/19 00:00 [pmc-release]
AID - 1750-2187-5-10 [pii]
AID - 10.1186/1750-2187-5-10 [doi]
PST - epublish
SO  - J Mol Signal. 2010 Jul 19;5:10. doi: 10.1186/1750-2187-5-10.