Suppression of pancreatic cancer by sulfated non-anticoagulant low molecular weight heparin.

Abstract

Sulfated non-anticoagulant heparins (S-NACHs) might be preferred for potential clinical use in cancer patients without affecting hemostasis as compared to low molecular weight heparins (LMWHs). We investigated anti-tumor effects, anti-angiogenesis effects, and mechanisms of S-NACH in a mouse model of pancreatic cancer as compared to the LMWH tinzaparin. S-NACH or tinzaparin with or without gemcitabine were administered, and tumor luminescent signal intensity, tumor weight, and histopathology were assessed at the termination of the study. S-NACH and LMWH efficiently inhibited tumor growth and metastasis, without any observed bleeding events with S-NACH as compared to tinzaparin. S-NACH distinctly increased tumor necrosis and enhanced gemcitabine response in the mouse pancreatic cancer models. These data suggest the potential implication of S-NACH as a neoadjuvant in pancreatic cancer.

• Authors: Thangirala Sudha, Murat Yalcin, Hung-Yun Lin, Ahmed M Elmetwally, Tipu Nazeer, Thiruvengadam Arumugam, Patricia Phillips, Shaker A Mousa
• Journal: Cancer letters (Cancer Lett) Vol. 350 Issue 1-2 Pg. 25-33 (Aug 01 2014) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 24769074 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Enzyme Inhibitors
• Fibrinolytic Agents
• Heparin, Low-Molecular-Weight
• Deoxycytidine
• Tinzaparin
• Gemcitabine

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Cell Line, Tumor
• Chick Embryo
• Chorioallantoic Membrane (drug effects)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• Female
• Fibrinolytic Agents (therapeutic use)
• Heparin, Low-Molecular-Weight (therapeutic use)
• Humans
• Mice
• Mice, Nude
• Neoplasm Metastasis
• Neovascularization, Pathologic (drug therapy)
• Pancreatic Neoplasms (drug therapy)
• Tinzaparin
• Xenograft Model Antitumor Assays
• Gemcitabine