PMID- 23056607
OWN - NLM
STAT- MEDLINE
DCOM- 20130531
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 10
DP  - 2012
TI  - Activation of AMP-activated protein kinase by 3,3'-Diindolylmethane (DIM) is 
      associated with human prostate cancer cell death in vitro and in vivo.
PG  - e47186
LID - 10.1371/journal.pone.0047186 [doi]
LID - e47186
AB  - There is a large body of scientific evidence suggesting that 
      3,3'-Diindolylmethane (DIM), a compound derived from the digestion of 
      indole-3-carbinol, which is abundant in cruciferous vegetables, harbors 
      anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that 
      AMP-activated protein kinase (AMPK) plays an essential role in cellular energy 
      homeostasis and tumor development and that targeting AMPK may be a promising 
      therapeutic option for cancer treatment in the clinic. We previously reported 
      that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher 
      bioavailability was able to induce apoptosis and inhibit cell growth, 
      angiogenesis, and invasion of prostate cancer cells. However, the precise 
      molecular mechanism(s) for the anti-cancer effects of B-DIM have not been fully 
      elucidated. In the present study, we investigated whether AMP-activated protein 
      kinase (AMPK) is a molecular target of B-DIM in human prostate cancer cells. Our 
      results showed, for the first time, that B-DIM could activate the AMPK signaling 
      pathway, associated with suppression of the mammalian target of rapamycin (mTOR), 
      down-regulation of androgen receptor (AR) expression, and induction of apoptosis 
      in both androgen-sensitive LNCaP and androgen-insensitive C4-2B prostate cancer 
      cells. B-DIM also activates AMPK and down-regulates AR in androgen-independent 
      C4-2B prostate tumor xenografts in SCID mice. These results suggest that B-DIM 
      could be used as a potential anti-cancer agent in the clinic for prevention 
      and/or treatment of prostate cancer regardless of androgen responsiveness, 
      although functional AR may be required.
FAU - Chen, Di
AU  - Chen D
AD  - Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State 
      University, School of Medicine, Detroit, Michigan, United States of America.
FAU - Banerjee, Sanjeev
AU  - Banerjee S
FAU - Cui, Qiuzhi C
AU  - Cui QC
FAU - Kong, Dejuan
AU  - Kong D
FAU - Sarkar, Fazlul H
AU  - Sarkar FH
FAU - Dou, Q Ping
AU  - Dou QP
LA  - eng
GR  - 5R01CA127258-05/CA/NCI NIH HHS/United States
GR  - 1R01CA120009/CA/NCI NIH HHS/United States
GR  - 3R01CA120009-04S1/CA/NCI NIH HHS/United States
GR  - R01 CA127258/CA/NCI NIH HHS/United States
GR  - R01 CA120009/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121009
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Indoles)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - SSZ9HQT61Z (3,3'-diindolylmethane)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Indoles/*pharmacology/*therapeutic use
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Prostatic Neoplasms/*drug therapy/*enzymology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC3467201
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/12 06:00
MHDA- 2013/06/01 06:00
PMCR- 2012/10/09
CRDT- 2012/10/12 06:00
PHST- 2012/03/05 00:00 [received]
PHST- 2012/09/13 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/06/01 06:00 [medline]
PHST- 2012/10/09 00:00 [pmc-release]
AID - PONE-D-12-06697 [pii]
AID - 10.1371/journal.pone.0047186 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(10):e47186. doi: 10.1371/journal.pone.0047186. Epub 2012 Oct 9.