cis-Hydroxyproline-mediated pancreatic carcinoma growth inhibition in mice
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
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.
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.
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.
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.
- Epstein RJ, Leung TW (2008) Tumor resensitization to erlotinib following brief substitution of cetuximab. Cancer Chemother Pharmacol 62:1111–1112 CrossRef
- Wong HH, Lemoine NR (2009) Pancreatic cancer: molecular pathogenesis and new therapeutic targets. Nat Rev Gastroenterol Hepatol 6:412–422 CrossRef
- Uggeri F, Caprotti R, De Grate L, Crippa S, Nobili C, Penati C, Romano F (2009) Short-term preoperative IL-2 immunotherapy in operable pancreatic cancer: a randomized study. Hepatogastroenterology 56:861–865
- Rivera F, López-Tarruella S, Vega-Villegas ME, Salcedo M (2009) Treatment of advanced pancreatic cancer: from gemcitabine single agent to combinations and targeted therapy. Cancer Treat Rev 35:335–339 CrossRef
- Oettle H, Neuhaus P (2007) Adjuvant therapy in pancreatic cancer: a critical appraisal. Drugs 67:2293–2310 CrossRef
- Rocha-Lima CM (2008) New directions in the management of advanced pancreatic cancer: a review. Anticancer Drugs 19:435–446 CrossRef
- Jaster R, Emmrich J (2008) Crucial role of fibrogenesis in pancreatic diseases. Best Pract Res Clin Gastroenterol 22:17–29 CrossRef
- Mahadevan D, Von Hoff DD (2007) Tumor–stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 6:1186–1197 CrossRef
- Rosenbloom J, Prockop DJ (1971) Incorporation of cis-hydroxyproline into protocollagen and collagen. Collagen containing cis-hydroxyproline in place of proline and trans-hydroxyproline is not extruded at a normal rate. J Biol Chem 25:1549–1555
- Yoo JS, Sakamoto T, Spee C, Kimura H, Harris MS, Hinton DR, Kay EP, Ryan SJ (1997) cis-Hydroxyproline inhibits proliferation, collagen synthesis, attachment, and migration of cultured bovine retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 38:520–528
- Mueller C, Emmrich J, Jaster R, Braun D, Liebe S, Sparmann G (2006) Cis-hydroxyproline-induced inhibition of pancreatic cancer cell growth is mediated by endoplasmic reticulum stress. World J Gastroenterol 12:1569–1576
- Corbett TH, Roberts BJ, Leopold WR, Peckham JC, Wilkoff LJ, Griswold DP Jr, Schabel FM Jr (1984) Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57BL/6 mice. Cancer Res 44:717–726
- Kulke MH, Blaszkowsky LS, Ryan DP et al (2007) Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol 20:4787–4792 CrossRef
- Stathopoulos GP, Androulakis N, Souglakos J, Stathopoulos J, Georgoulias V (2008) Present treatment and future expectations in advanced pancreatic cancer. Anticancer Res 28:1303–1338
- Ciardiello F, Sanfilippo B, Yanagihara K et al (1988) Differential growth sensitivity to 4-cis-hydroxy-l-proline of transformed rodent cell lines. Cancer Res 48:2483–2491
- Priebe TS, Atkinson EN, Pan BF, Nelson JA (1992) Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma PANC02. Cancer Chemother Pharmacol 29:485–489 CrossRef
- Maletzki C, Linnebacher M, Kreikemeyer B, Emmrich J (2008) Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model. Gut 57:483–591 CrossRef
- Ziske C, Tiemann K, Schmidt T et al (2008) Real-time high-resolution compound imaging allows percutaneous initiation and surveillance in an orthotopic murine pancreatic cancer model. Pancreas 36:146–152 CrossRef
- Aikawa T, Gunn J, Spong SM, Klaus SJ, Korc M (2006) Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther 5:1108–1116 CrossRef
- Buck TB, Hall AL, Sinha CC, Bunce OR, Thorgeirsson UP (2000) cis-Hydroxyproline stimulates the growth of rat mammary carcinoma cells. In Vivo 14:7–11
- cis-Hydroxyproline-mediated pancreatic carcinoma growth inhibition in mice
International Journal of Colorectal Disease
Volume 25, Issue 8 , pp 921-929
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Pancreatic cancer
- Growth inhibition
- Mouse model
- Industry Sectors