Heparin induces apoptosis through suppression of AKt in oral squamous cell carcinoma cells.
BACKGROUND
Heparin is a polysulfated glycosaminoglycan that has been shown to have antiproliferative and apoptotic effects in addition to its anticoagulant effects.


METHODS
The present work investigated the effects of unfractioned heparin (UFH) on cell growth and apoptosis in four oral squamous cell carcinoma (SCC) cell lines and the mechanism(s) underlying its actions using MTT assay, Annexin-V-FITC and Western blotting.


RESULTS
Treatment with UFH resulted in significant reduction in cell viability and increase in apoptosis in three of the four tested cell lines. Further, such treatment resulted in a significant decrease in phosphorylated AKt, and consequently led to activation of the mitochondrial pathway in heparin-sensitive cells. Moreover, pretreatment with UFH significantly increased the apoptosis induced by cisplatin.


CONCLUSIONS
These findings indicate that heparin induces apoptosis through suppression of AKt, and suggest a potential utility of heparin for development of less toxic chemotherapy in treatment of oral SCC.
Ueda
Kohei
K
Department of Oral and Maxillofacial Surgery, Toyama University, 2630 Sugitani, Toyama 930-0194, Japan.
Inoue
Shuichi
S
Zhang
Ye
Y
Kutsuna
Tomohiko
T
Inoue
Sayaka
S
Noto
Kumiko
K
Arai
Naoya
N
Noguchi
Makoto
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D051025:bcl-Associated Death Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C494819:BAD protein, human; D005343:Fibrinolytic Agents; D051025:bcl-Associated Death Protein; D006493:Heparin; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin