Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis

Bin Li, Colin A. Flaveny, Camilla Giambelli, Dennis Liang Fei, Lu Han, Brian I. Hang, Feng Bai, Xin-Hai Pei, Vania Nose, Oname Burlingame, Anthony J Capobianco, Darren Orton, Ethan Lee, David J Robbins

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC) promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP) and 85% of spontaneous colorectal cancers (CRC). FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

Original languageEnglish
Article numbere101969
JournalPLoS One
Volume9
Issue number7
DOIs
StatePublished - Jul 8 2014

Fingerprint

Intestinal Polyposis
Enterobius
Adenomatous Polyposis Coli
colorectal neoplasms
adenoma
drugs
Pharmaceutical Preparations
Chemical activation
mice
Colorectal Neoplasms
oral administration
agonists
biomarkers
Adenoma
Biomarkers
animal models
Enterobiasis
mutation
pyrvinium
Oral Administration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis. / Li, Bin; Flaveny, Colin A.; Giambelli, Camilla; Liang Fei, Dennis; Han, Lu; Hang, Brian I.; Bai, Feng; Pei, Xin-Hai; Nose, Vania; Burlingame, Oname; Capobianco, Anthony J; Orton, Darren; Lee, Ethan; Robbins, David J.

In: PLoS One, Vol. 9, No. 7, e101969, 08.07.2014.

Research output: Contribution to journalArticle

Li, B, Flaveny, CA, Giambelli, C, Liang Fei, D, Han, L, Hang, BI, Bai, F, Pei, X-H, Nose, V, Burlingame, O, Capobianco, AJ, Orton, D, Lee, E & Robbins, DJ 2014, 'Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis', PLoS One, vol. 9, no. 7, e101969. https://doi.org/10.1371/journal.pone.0101969
Li, Bin ; Flaveny, Colin A. ; Giambelli, Camilla ; Liang Fei, Dennis ; Han, Lu ; Hang, Brian I. ; Bai, Feng ; Pei, Xin-Hai ; Nose, Vania ; Burlingame, Oname ; Capobianco, Anthony J ; Orton, Darren ; Lee, Ethan ; Robbins, David J. / Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis. In: PLoS One. 2014 ; Vol. 9, No. 7.
@article{dc0a2bde6c9d4cee9225c0755acd9cff,
title = "Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis",
abstract = "Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC) promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP) and 85{\%} of spontaneous colorectal cancers (CRC). FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.",
author = "Bin Li and Flaveny, {Colin A.} and Camilla Giambelli and {Liang Fei}, Dennis and Lu Han and Hang, {Brian I.} and Feng Bai and Xin-Hai Pei and Vania Nose and Oname Burlingame and Capobianco, {Anthony J} and Darren Orton and Ethan Lee and Robbins, {David J}",
year = "2014",
month = "7",
day = "8",
doi = "10.1371/journal.pone.0101969",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis

AU - Li, Bin

AU - Flaveny, Colin A.

AU - Giambelli, Camilla

AU - Liang Fei, Dennis

AU - Han, Lu

AU - Hang, Brian I.

AU - Bai, Feng

AU - Pei, Xin-Hai

AU - Nose, Vania

AU - Burlingame, Oname

AU - Capobianco, Anthony J

AU - Orton, Darren

AU - Lee, Ethan

AU - Robbins, David J

PY - 2014/7/8

Y1 - 2014/7/8

N2 - Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC) promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP) and 85% of spontaneous colorectal cancers (CRC). FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

AB - Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC) promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP) and 85% of spontaneous colorectal cancers (CRC). FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

UR - http://www.scopus.com/inward/record.url?scp=84903895414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903895414&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0101969

DO - 10.1371/journal.pone.0101969

M3 - Article

C2 - 25003333

AN - SCOPUS:84903895414

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e101969

ER -