Suppression of pancreatic cancer by sulfated non-anticoagulant low molecular weight heparin.
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.
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
Thangirala
T
Sudha
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA; Department of Physiology, Veterinary Medicine Faculty, Uludag University, Gorukle, Bursa, Turkey.
Murat
M
Yalcin
Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
Hung-Yun
HY
Lin
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
Ahmed M
AM
Elmetwally
Department of Pathology, Albany Medical College, Albany, NY, USA.
Tipu
T
Nazeer
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Thiruvengadam
T
Arumugam
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
Patricia
P
Phillips
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA. Electronic address: shaker.mousa@acphs.edu.
Shaker A
SA
Mousa
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000078222:Tinzaparin; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D003841:Deoxycytidine; D000078222:Tinzaparin; D000093542:Gemcitabine
Anti-cancer; Low molecular weight heparin; Non-anticoagulant heparin; Pancreatic cancer; Tumor suppressor; Tumor survival