Studies On The Differentiation Of Cancer Cell Lines Induced By S86019 And Its Mechanism Of Action

S86019 is an active principle of Pueraria Lobata which was used as an antihypertensive drug traditionally. Through a routine screening program with promyelocytic leukemia cell (HL-60), it was found that S86019 was able to induce cell differentiation of HL-60 cells in vitro and it had synergistic effect with retinoid (N—4—carboxyphenyl retinamide; RII) on the induced differentiation of HL-60 cells. The effects of S86019 on the induction of cell differentiation of a series of cancer cell lines and the mechanism of action of this compound were studied in this thesis.The results showed that HL—60 cells were induced to differentiate along granulocyte lineage by S86019 at a concentration of 20 μg/ ml in vitro.Sixty percent of the HL-60 cells treated by S86019 exhibited NBT reduction and phagocytosis activity. The activity of acid phosphatase in the treated HL-60 cells was increased significantly and the treated cells turned to be matured morphologically. Most of the matured cells were in myelocytic or metamyelocytic stage and a few of the cells were in banded or segmented stage.When lower concentration of S86019 was given in combination with Bc—4, an active principle from Boswellia carteria or Ara—c, the induction activity was increased and showed synergistic effect and the cells differentiated into granulocytes. Flow cytometry had proved that the cells treated with S86019 at a concentration of 20 μg/ ml or 10 μg/ml of S86019 in combination with Bc-4 5 μg/ ml or Ara-c 0.06 μg/ ml were blocked in G1 phase. The number of cells in Gl phase was increased significantly.By using the subrenal capsule assay (SRCA) and diffusion chamber transplanted into peritoneal cavity of mouse, it was shown that the growth of HL-60 cells in SRC and diffusion chamber was inhibited significantly by S86019 at a dosage of 50 mg/ kg, The relative tumor volume in the group treated by S86019 were smaller than that of control group in SRC and 60% of the cells treated by S86019 exhibited NBT reduction and matured phenotype; while only 20% of the cells in control group exhibited NBT positive . The cell number and the colony number of HL-60 cells grown in diffusion chambers in mouse peritoneal cavity were decreased in the treated group. Sixty percent of the cells in treated...