Thrombospondin-1 induces apoptosis in primary leukemia and cell lines mediated by CD36 and Caspase-3

Int J Mol Med. 2003 Dec;12(6):995-1001.

Abstract

Thrombospondin-1 (TSP-1) is a naturally occurring anti-angiogenic compound that induces apoptosis of endothelial and cancer cells via its receptor CD36. The objectives of our study were to investigate the in vitro effects of TSP-1 on the apoptosis of primary human leukemia cells as well as leukemia cell lines and the possible mechanism involving CD36. Our results demonstrated that TSP-1 induced apoptosis in CD36 positive cell lines CHRF-288-11, Meg-01 and HL-60, but not CD36 negative K562, at a dose-dependent manner as demonstrated by DNA ladder formation, Annexin V and propidium iodide (PI) stainings. The addition of anti-CD36 antibody FA6-152 or thrombopoietin (TPO) significantly nullified the effects of TSP-1. TSP-1-mediated apoptosis was consistently associated with the up-regulation of active Caspase-3. Responses of 2 CD36 positive primary AML samples to TSP-1 and FA6-152 were similar with those of leukemia cell lines. TSP-1 significantly induced apoptosis in B-ALL but the counter-effects of FA6-152 were less apparent. CD36 negative AML cells appeared less susceptible to TSP-1 and FA6-152. Our data provided strong evidence that TSP-1 exerted direct apoptotic effects on leukemia cells and could be developed as an adjunct to conventional therapy, particularly for leukemia cells that express CD36 or other TSP-1 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • CD36 Antigens / drug effects
  • Caspase 3
  • Caspases / drug effects
  • Cell Division / drug effects
  • Humans
  • Leukemia / drug therapy*
  • Thrombospondin 1 / pharmacology*

Substances

  • Antineoplastic Agents
  • CD36 Antigens
  • Thrombospondin 1
  • CASP3 protein, human
  • Caspase 3
  • Caspases