The hepoxilin analog, PBT-3, inhibits growth of K-562 CML solid tumours in vivo in nude mice.
PBT-3 is one of a family of stable chemical analogs of the hepoxilins, products derived from arachidonic acid. We previously showed that PBT-3 caused apoptosis in the chronic myelogenous leukemia (CML) cell line K-562 in vitro (Anti-cancer Res 23: 3617-3622, 2003). It was as effective as Gleevec, a novel agent that blocks tyrosine kinase activity during treatment of CML. We describe, herein, the growth inhibiting effects of PBT-3 in nude mice into which K-562 cells were transplanted subcutaneously. Groups of mice were treated with vehicle as control, or PBT-3, or Gleevec. PBT-3 was effective during the 8-day treatment protocol in inhibiting the growth of the tumours in vivo as was Gleevec. Analysis of the tumours demonstrated the presence of apoptosis (DNA laddering and TUNEL assay) in both the PBT-3- and Gleevec-treated groups. These results demonstrate that PBT-3 is effective in vivo in controlling tumour growth and provides a novel platform for the therapeutic control of cancer.
Li
Xiang
X
Research Institute Programs in Integrative Biology, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.
Qiao
Na
N
Reynaud
Denis
D
Abdelhaleem
Mohamed
M
Pace-Asciak
Cecil R
CR
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D000068877:Imatinib Mesylate; D007279:Injections, Subcutaneous; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013997:Time Factors; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D001549:Benzamides; D006131:Growth Inhibitors; C453725:PBT-3 compound; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D015126:8,11,14-Eicosatrienoic Acid