In the present study, the apoptotic mechanism and polyamine transporter recognition of WJH-6,  a novel polyamine conjugate, were investigated in K562 and HL-60 cells.  The cytotoxicity of WJH-6 was   assessed by MTT assay; cell cycle distribution and apoptosis were measured by flow cytometry; the protein  expression of Caspase-3, Caspase-8, Caspase-9, Bid and mitochondrial membrane potential (MMP) were evaluated by high content screening (HCS) analysis; the protein expression of cytochrome c was measured by Western blotting.  The results showed that WJH-6 could be recognized and transported by polyamine transporter (PAT).  Furthermore, WJH-6 was able to inhibit K562 and HL-60 cells proliferation and induce apoptosis.  This   apoptotic effect was relative to MMP loss, cytochrome c release from mitochondria to cytoplasm and the     activation of Caspase-8, Caspase-9, Caspase-3 and Bid.  These results suggested that WJH-6-induced K562 and HL-60 cells apoptosis was related with mitochondrial damage.