Thrombospondin-1 induces apoptosis in primary leukemia and cell lines mediated by CD36 and Caspase-3.
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.
Li
Karen
K
Department of Paediatrics, Prince of Wales Hospital, Shatin, N.T., Hong Kong. lipang@cuhk.edu.hk
Yang
Mo
M
Yuen
Patrick Man Pan
PM
Chik
Ki Wai
KW
Li
Chi Kong
CK
Shing
Matthew Ming Kong
MM
Lam
Hubert Kin Bong
HK
Fok
Tai Fai
TF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018955:CD36 Antigens / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D019700:Thrombospondin 1 / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018955:CD36 Antigens; D019700:Thrombospondin 1; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases