Targeting the hedgehog signaling pathway with interacting peptides to Patched-1

Masafumi Nakamura, Haruo Tanaka, Yousuke Nagayoshi, Hiroshi Nakashima, Kosuke Tsutsumi, Ohtsuka Takao, Shunichi Takahata, Masao Tanaka, Hidechika Okada

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: The hedgehog (Hh) signaling pathway is aberrantly activated in many cancers. Overproduction of sonic hedgehog (Shh), a ligand in the Hh pathway, increases Hh signaling activity by inhibiting Patched-1 (Ptch1), a suppressive receptor in the Hh pathway. The purpose of this study was to establish a novel strategy for treating pancreatic cancer and other Hh-dependent cancers through control of the tumor-suppressive function of Ptch1. Methods: We synthesized seven interacting peptides to the amino-acid sequence of the Ptch1 docking site for Shh. Human pancreatic cancer cell lines (AsPC-1, SUIT2) were cultured in the presence or absence of the peptides. Cell proliferation was assessed by cell counting and by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The activity of the Hh pathway was estimated by real-time polymerase chain reaction of the target gene product Gli1. To confirm their anti-tumor activity in vivo, the effect of the peptides in a mouse model of pancreatic cancer was determined. Finally, the Hh signaling activity of the xenograft was examined. Results: Three of the interacting peptides to Ptch1 suppressed the proliferation of the two pancreatic cancer cell lines and decreased the expression of Gli1, both in vitro and in vivo. Conclusions: This study suggests that interacting peptides to Ptch1 may be a new tool for controlling the Hh-dependent growth of pancreatic cancer.

Original languageEnglish
Pages (from-to)452-460
Number of pages9
JournalJournal of Gastroenterology
Volume47
Issue number4
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Hedgehogs
Peptides
Pancreatic Neoplasms
Neoplasms
Cell Line
Heterografts
Real-Time Polymerase Chain Reaction
Amino Acid Sequence
Cell Proliferation
Ligands

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Targeting the hedgehog signaling pathway with interacting peptides to Patched-1. / Nakamura, Masafumi; Tanaka, Haruo; Nagayoshi, Yousuke; Nakashima, Hiroshi; Tsutsumi, Kosuke; Takao, Ohtsuka; Takahata, Shunichi; Tanaka, Masao; Okada, Hidechika.

In: Journal of Gastroenterology, Vol. 47, No. 4, 04.2012, p. 452-460.

Research output: Contribution to journalArticle

Nakamura, M, Tanaka, H, Nagayoshi, Y, Nakashima, H, Tsutsumi, K, Takao, O, Takahata, S, Tanaka, M & Okada, H 2012, 'Targeting the hedgehog signaling pathway with interacting peptides to Patched-1', Journal of Gastroenterology, vol. 47, no. 4, pp. 452-460. https://doi.org/10.1007/s00535-011-0507-6
Nakamura, Masafumi ; Tanaka, Haruo ; Nagayoshi, Yousuke ; Nakashima, Hiroshi ; Tsutsumi, Kosuke ; Takao, Ohtsuka ; Takahata, Shunichi ; Tanaka, Masao ; Okada, Hidechika. / Targeting the hedgehog signaling pathway with interacting peptides to Patched-1. In: Journal of Gastroenterology. 2012 ; Vol. 47, No. 4. pp. 452-460.
@article{f00bd0e9c7374136b4ec93361d244ec7,
title = "Targeting the hedgehog signaling pathway with interacting peptides to Patched-1",
abstract = "Background: The hedgehog (Hh) signaling pathway is aberrantly activated in many cancers. Overproduction of sonic hedgehog (Shh), a ligand in the Hh pathway, increases Hh signaling activity by inhibiting Patched-1 (Ptch1), a suppressive receptor in the Hh pathway. The purpose of this study was to establish a novel strategy for treating pancreatic cancer and other Hh-dependent cancers through control of the tumor-suppressive function of Ptch1. Methods: We synthesized seven interacting peptides to the amino-acid sequence of the Ptch1 docking site for Shh. Human pancreatic cancer cell lines (AsPC-1, SUIT2) were cultured in the presence or absence of the peptides. Cell proliferation was assessed by cell counting and by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The activity of the Hh pathway was estimated by real-time polymerase chain reaction of the target gene product Gli1. To confirm their anti-tumor activity in vivo, the effect of the peptides in a mouse model of pancreatic cancer was determined. Finally, the Hh signaling activity of the xenograft was examined. Results: Three of the interacting peptides to Ptch1 suppressed the proliferation of the two pancreatic cancer cell lines and decreased the expression of Gli1, both in vitro and in vivo. Conclusions: This study suggests that interacting peptides to Ptch1 may be a new tool for controlling the Hh-dependent growth of pancreatic cancer.",
author = "Masafumi Nakamura and Haruo Tanaka and Yousuke Nagayoshi and Hiroshi Nakashima and Kosuke Tsutsumi and Ohtsuka Takao and Shunichi Takahata and Masao Tanaka and Hidechika Okada",
year = "2012",
month = "4",
doi = "10.1007/s00535-011-0507-6",
language = "English",
volume = "47",
pages = "452--460",
journal = "Journal of Gastroenterology",
issn = "0944-1174",
publisher = "Springer Japan",
number = "4",

}

TY - JOUR

T1 - Targeting the hedgehog signaling pathway with interacting peptides to Patched-1

AU - Nakamura, Masafumi

AU - Tanaka, Haruo

AU - Nagayoshi, Yousuke

AU - Nakashima, Hiroshi

AU - Tsutsumi, Kosuke

AU - Takao, Ohtsuka

AU - Takahata, Shunichi

AU - Tanaka, Masao

AU - Okada, Hidechika

PY - 2012/4

Y1 - 2012/4

N2 - Background: The hedgehog (Hh) signaling pathway is aberrantly activated in many cancers. Overproduction of sonic hedgehog (Shh), a ligand in the Hh pathway, increases Hh signaling activity by inhibiting Patched-1 (Ptch1), a suppressive receptor in the Hh pathway. The purpose of this study was to establish a novel strategy for treating pancreatic cancer and other Hh-dependent cancers through control of the tumor-suppressive function of Ptch1. Methods: We synthesized seven interacting peptides to the amino-acid sequence of the Ptch1 docking site for Shh. Human pancreatic cancer cell lines (AsPC-1, SUIT2) were cultured in the presence or absence of the peptides. Cell proliferation was assessed by cell counting and by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The activity of the Hh pathway was estimated by real-time polymerase chain reaction of the target gene product Gli1. To confirm their anti-tumor activity in vivo, the effect of the peptides in a mouse model of pancreatic cancer was determined. Finally, the Hh signaling activity of the xenograft was examined. Results: Three of the interacting peptides to Ptch1 suppressed the proliferation of the two pancreatic cancer cell lines and decreased the expression of Gli1, both in vitro and in vivo. Conclusions: This study suggests that interacting peptides to Ptch1 may be a new tool for controlling the Hh-dependent growth of pancreatic cancer.

AB - Background: The hedgehog (Hh) signaling pathway is aberrantly activated in many cancers. Overproduction of sonic hedgehog (Shh), a ligand in the Hh pathway, increases Hh signaling activity by inhibiting Patched-1 (Ptch1), a suppressive receptor in the Hh pathway. The purpose of this study was to establish a novel strategy for treating pancreatic cancer and other Hh-dependent cancers through control of the tumor-suppressive function of Ptch1. Methods: We synthesized seven interacting peptides to the amino-acid sequence of the Ptch1 docking site for Shh. Human pancreatic cancer cell lines (AsPC-1, SUIT2) were cultured in the presence or absence of the peptides. Cell proliferation was assessed by cell counting and by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The activity of the Hh pathway was estimated by real-time polymerase chain reaction of the target gene product Gli1. To confirm their anti-tumor activity in vivo, the effect of the peptides in a mouse model of pancreatic cancer was determined. Finally, the Hh signaling activity of the xenograft was examined. Results: Three of the interacting peptides to Ptch1 suppressed the proliferation of the two pancreatic cancer cell lines and decreased the expression of Gli1, both in vitro and in vivo. Conclusions: This study suggests that interacting peptides to Ptch1 may be a new tool for controlling the Hh-dependent growth of pancreatic cancer.

UR - http://www.scopus.com/inward/record.url?scp=84863087715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863087715&partnerID=8YFLogxK

U2 - 10.1007/s00535-011-0507-6

DO - 10.1007/s00535-011-0507-6

M3 - Article

C2 - 22170414

AN - SCOPUS:84863087715

VL - 47

SP - 452

EP - 460

JO - Journal of Gastroenterology

JF - Journal of Gastroenterology

SN - 0944-1174

IS - 4

ER -