International Journal of Colorectal Disease

, Volume 25, Issue 8, pp 921–929

cis-Hydroxyproline-mediated pancreatic carcinoma growth inhibition in mice

  • Dietrich Sturm
  • Claudia Maletzki
  • Dagmar Braun
  • Joerg Emmrich
Original Article

Abstract

Purpose

This study addressed the question of whether the collagen metabolism modulator cis-4-Hydroxy-l-proline (CHP) is applicable for potential use as a therapeutic inhibitor of pancreatic carcinoma cell growth.

Methods

Cell proliferation, as well as quantification of apoptosis of murine Panc02 cells, was assessed after CHP treatment. Supplementary, the effect of CHP on tumor growth was examined in the subcutaneous Panc02 model in vivo. Mice received daily intraperitoneal injections of CHP (300, 400, and 500 mg/kg bw). In addition to the assessment of systemic parameters (blood count, enzyme activities), histology (HE) and immunohistochemistry (Ki-67) were performed from resected tumor specimens.

Results

Like reduction of metabolic activity, CHP also induced inhibition of cell growth in a dose-dependent manner, with however only slight increases in apoptosis. In vivo treatment of Panc02 tumors with CHP resulted in pronounced delay of tumor growth and decreases in tumor cell proliferation. Moreover, these effects were accompanied by a massive systemic leukocytosis as well increased leukocyte infiltration into the tumors subsequent to CHP therapy.

Conclusions

CHP inhibits the proliferation of Panc02 tumor cells in a dose-dependent manner both in vitro and in vivo. Our presented data show that modulation of the collagen metabolism is an interesting strategy for treatment of pancreatic carcinoma.

Keywords

cis-Hydroxyproline Pancreatic cancer Growth inhibition Mouse model 

Abbreviations

CHP

cis-4-Hydroxy-l-proline

i.p.

Intraperitoneal

PBL

Peripheral blood leukocytes

ASAT

Aspartate aminotransferase

ALAT

Alanine transaminase

LDH

Lactate dehydrogenase

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Dietrich Sturm
    • 1
  • Claudia Maletzki
    • 1
  • Dagmar Braun
    • 2
  • Joerg Emmrich
    • 1
  1. 1.Division of Gastroenterology, Department of Internal MedicineUniversity of RostockRostockGermany
  2. 2.Riemser Arzneimittel AGGreifswaldGermany

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