PMID- 20395211
OWN - NLM
STAT- MEDLINE
DCOM- 20100428
LR  - 20150615
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 8
DP  - 2010 Apr 15
TI  - Common botanical compounds inhibit the hedgehog signaling pathway in prostate 
      cancer.
PG  - 3382-90
LID - 10.1158/0008-5472.CAN-09-3012 [doi]
AB  - Many botanical compounds have been proposed to prevent cancer. We investigated 
      the cancer treatment and prevention abilities of apigenin, baicalein, curcumin, 
      epigallocatechin 3-gallate (EGCG), genistein, quercetin, and resveratrol both in 
      vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice as well as 
      in vitro in prostate cancer cell lines. In our experiments, these seven compounds 
      act similarly to the Hedgehog antagonist cyclopamine, a teratogenic plant 
      alkaloid, which had been previously shown to "cure" prostate cancer in a mouse 
      xenograft model. With IC(50) values ranging from <1 to 25 mumol/L, these 
      compounds can inhibit Gli1 mRNA concentration by up to 95% and downregulate Gli 
      reporter activity by 80%. We show that four compounds, genistein, curcumin, EGCG, 
      and resveratrol, inhibit Hedgehog signaling as monitored by real-time reverse 
      transcription-PCR analysis of Gli1 mRNA concentration or by Gli reporter 
      activity. Three compounds, apigenin, baicalein, and quercetin, decreased Gli1 
      mRNA concentration but not Gli reporter activity. Our results show that these 
      compounds are also able to reduce or delay prostate cancer in vivo in TRAMP mice. 
      All seven compounds, when fed in combination as pure compounds or as crude plant 
      extracts, inhibit well-differentiated carcinoma of the prostate by 58% and 81%, 
      respectively. In vitro, we show that all seven compounds also inhibit growth in 
      human and mouse prostate cancer cell lines. Mechanistically, we propose the 
      Hedgehog signaling pathway to be a direct or indirect target of these compounds. 
      These botanicals at pharmacologic concentrations are potentially safer and less 
      expensive alternatives to cyclopamine and its pharmaceutical analogues for cancer 
      therapy.
CI  - (c) 2010 AACR.
FAU - Slusarz, Anna
AU  - Slusarz A
AD  - Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, 
      USA.
FAU - Shenouda, Nader S
AU  - Shenouda NS
FAU - Sakla, Mary S
AU  - Sakla MS
FAU - Drenkhahn, Sara K
AU  - Drenkhahn SK
FAU - Narula, Acharan S
AU  - Narula AS
FAU - MacDonald, Ruth S
AU  - MacDonald RS
FAU - Besch-Williford, Cynthia L
AU  - Besch-Williford CL
FAU - Lubahn, Dennis B
AU  - Lubahn DB
LA  - eng
GR  - R01AT002978/AT/NCCIH NIH HHS/United States
GR  - R0I-ES 510535/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Hedgehog Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor, Member 25)
RN  - 0 (TNFRSF25 protein, human)
RN  - 0 (Tnfrsf25 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Hedgehog Proteins/*metabolism
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phytotherapy/methods
MH  - Prostatic Neoplasms/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Tumor Necrosis Factor, Member 25/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Signal Transduction
EDAT- 2010/04/17 06:00
MHDA- 2010/04/29 06:00
CRDT- 2010/04/17 06:00
PHST- 2010/04/17 06:00 [entrez]
PHST- 2010/04/17 06:00 [pubmed]
PHST- 2010/04/29 06:00 [medline]
AID - 70/8/3382 [pii]
AID - 10.1158/0008-5472.CAN-09-3012 [doi]
PST - ppublish
SO  - Cancer Res. 2010 Apr 15;70(8):3382-90. doi: 10.1158/0008-5472.CAN-09-3012.