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Pentosan polysulfate, a potent anti HIV and anti tumor agent, inhibits protein serine/threonine and tyrosine kinases

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Abstract

Pentosan polysulfate, a polyanionic mucopolysaccharide, which has been shown to exert inhibitory effects on human immunodeficiency virus (HIV-I) replication, inhibited the activities of protein tyrosine kinases from lymphocytes (Jurkat cells) and rat lung in a concentration dependent manner. In addition, the autophosphorylation of p56lck, a lymphocyte associated protein tyrosine kinase from Jurkat cells was also inhibited by pentosan polysulfate (100μg/ml). Furthermore, the activities of protein serine/threonine kinases such as Ca2+, phospholipid-dependent protein kinase (protein kinase C) from human platelets and the catalytic subunit of cAMP-dependent protein kinase from skeletal muscle were also inhibited by this mucopolysaccharide. However, the activity of phosphorylase kinase was not altered. The inhibition of rat lung protein tyrosine kinase was rapid and competitive with respect to ATP with an apparent Ki value of 5–20μg/ml. These results suggest that the ability of pentosan polysulfate to inhibit various protein serine/threonine and tyrosine kinases may be one of the mechanisms by which this compound exerts its inhibitory effect of HIV-I replication. (Mol Cell Biochem120: 127–133, 1993)

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Abbreviations

HIV:

Human Immunodeficiency Virus

PPS:

Pentosan Polysulfate

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Authors and Affiliations

  1. Clinical Research Institute of Montreal, Departments of Medicine, University of Montreal, 110 Pine Avenue West, H2W 1R7, Montréal, Québec, Canada

    Ashok K. Srivastava & Jean-Louis Chiasson

  2. Microbiology & Immunology, University of Montreal, 110 Pine Avenue West, H2W 1R7, Montréal, Québec, Canada

    Rafick-Pierre Sékaly

Authors
  1. Ashok K. Srivastava
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  2. Rafick-Pierre Sékaly
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  3. Jean-Louis Chiasson
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Srivastava, A.K., Sékaly, RP. & Chiasson, JL. Pentosan polysulfate, a potent anti HIV and anti tumor agent, inhibits protein serine/threonine and tyrosine kinases. Mol Cell Biochem 120, 127–133 (1993). https://doi.org/10.1007/BF00926085

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  • DOI: https://doi.org/10.1007/BF00926085

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