Thrombin induces apoptosis in human tumor cells

Rasheed Ahmad, Laurent Knafo, Jingwu Xu, Sardar Sindhu, José Menezes, Ali Ahmad

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Thrombin is a serine protease that is produced during the coagulation process and plays an essential role for hemostasis, thrombosis and wound healing. It is a potent activator of platelets, induces proliferation of a wide variety of normal and malignant human cells, and enhances their invasiveness and metastatic potential. We studied the effect of thrombin on the proliferation of a wide variety of human tumor cells and report here that, at low concentrations, thrombin induces proliferation of these cells. However, at higher concentrations, thrombin inhibited their proliferation. We show that this inhibition of cell proliferation was due to apoptosis of the tumor cells. The thrombin-mediated apoptosis was inhibited significantly by its specific inhibitor, hirudin. Furthermore, no consistent pattern of induction and/or modulation of p53, p21 and bcl-2 was observed in the thrombin-mediated apoptosis. To our knowledge, this is the first report to describe the pro-apoptotic effects of thrombin on human tumor ceils and may have implications for chemotherapy in cancer patients and for the pathogenesis of AIDS as well. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)707-715
Number of pages9
JournalInternational Journal of Cancer
Volume87
Issue number5
DOIs
Publication statusPublished - 24 Aug 2000

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