10.1158/1535-7163.MCT-15-0861 http://scihub22266oqcxt.onion/10.1158/1535-7163.MCT-15-0861 C5096967!5096967
!27474149
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Mol+Cancer+Ther
2016 ; 15
(11
): 2791-2801
Nephropedia Template TP gab.com Text Twit Text FOAVip Twit Text # English Wikipedia
Wedelolactone, an Anti-inflammatory Botanical, Interrupts c-Myc Oncogenic
Signaling and Synergizes with Enzalutamide to Induce Apoptosis in Prostate Cancer
Cells
#MMPMID27474149
Sarveswaran S
; Ghosh R
; Parikh R
; Ghosh J
Mol Cancer Ther
2016[Nov]; 15
(11
): 2791-2801
PMID27474149
show ga
The c-Myc gene encodes an oncoprotein transcription factor that is frequently
upregulated in almost all cancer types and is the subject of intense
investigation for management of cancer because of its pleiotropic effects
controlling a spectrum of cellular functions. However, due of its nonenzymatic
nature, development of suitable strategies to block its protein-protein or
protein-DNA interaction is challenging. Thus, c-Myc has been recognized as an
elusive molecular target for cancer control, and various approaches are in
development to inhibit c-Myc transcriptional activity. We observed that
wedelolactone (WDL), an anti-inflammatory botanical compound, severely
downregulates the expression of c-Myc mRNA in prostate cancer cells. Moreover,
WDL dramatically decreases the protein level, nuclear accumulation, DNA-binding,
and transcriptional activities of c-Myc. c-Myc is a transforming oncogene widely
expressed in prostate cancer cells and is critical for maintaining their
transformed phenotype. Interestingly, WDL was found to strongly affect the
viability of Myc-activated prostate cancer cells and completely block their
invasion as well as soft agar colony formation in vitro WDL was also found to
downregulate c-Myc in vivo in nude mice xenografts. Moreover, WDL synergizes with
enzalutamide to decrease the viability of androgen-sensitive prostate cancer
cells via induction of apoptosis. These findings reveal a novel anticancer
mechanism of the natural compound WDL, and suggest that the oncogenic function of
c-Myc in prostate cancer cells can be effectively downregulated by WDL for the
development of a new therapeutic strategy against Myc-driven prostate cancer. Mol
Cancer Ther; 15(11); 2791-801. ©2016 AACR.
Please enable JavaScript to view the comments powered by Disqus. |Animals
[MESH] |Apoptosis/*drug effects
[MESH] |Benzamides
[MESH] |Cell Line, Tumor
[MESH] |Cell Survival/drug effects
[MESH] |Coumarins/*pharmacology
[MESH] |Disease Models, Animal
[MESH] |Drug Synergism
[MESH] |Gene Expression Regulation, Neoplastic/drug effects
[MESH] |Humans
[MESH] |Male
[MESH] |Mice
[MESH] |Neoplastic Stem Cells/drug effects/metabolism
[MESH] |Nitriles
[MESH] |Phenylthiohydantoin/*analogs & derivatives/pharmacology
[MESH] |Prostatic Neoplasms/genetics/*metabolism
[MESH] |Protein Transport
[MESH] |Proto-Oncogene Proteins c-myc/genetics/*metabolism
[MESH] |Signal Transduction/*drug effects
[MESH] |Tumor Stem Cell Assay
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