Effects of 1-methyl-3-propyl-7-butylxanthine (MPBX) on idarubicin-induced antitumor activity and bone marrow suppression

The effects of 1-methyl-3-propyl-7-butylxanthine (MPBX), a xanthine derivat ive, on idarubicin (IDA)-induced antitumor activity against P388 leukemia c ells (P388) and bone marrow suppression were examined, In P388 tumor-bearin g mice, the combination of MPBX with LDA increased the antitumor activity o f IDA. The IDA. concentration in the tumors in the MPBX combination group i ncreased by 2.0-fold compared to the level in the IDA-alone group. On the o ther hand, as regards LDA-induced bone marrow suppression, the combination of MPBX with IDA reduced the decrease in the bone marrow cell number by 30% compared to that in the IDA-alone group. In addition, the IDA concentratio n in the bone marrow cells was decreased by the combination of MPBX with ID A, An in vitro experiment showed that MPBX facilitated IDA influx and suppr essed IDA efflux in P388 cells, In conclusion, the combination of MPBX with IDA increased the antitumor activity and decreased the bone marrow suppres sion, Therefore, we expect that the combination of MPBX with IDA will be us eful for leukemia chemotherapy.