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 derivative, on idarubicin (IDA)-induced antitumor activity against P388 leukemia cells (P388) and bone marrow suppression were examined. In P388 tumor-bearing mice, the combination of MPBX with IDA increased the antitumor activity of IDA. The IDA concentration in the tumors in the MPBX combination group increased by 2.0-fold compared to the level in the IDA-alone group. On the other hand, as regards IDA-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 concentration in the bone marrow cells was decreased by the combination of MPBX with IDA. An in vitro experiment showed that MPBX facilitated IDA influx and suppressed IDA efflux in P388 cells. In conclusion, the combination of MPBX with IDA increased the antitumor activity and decreased the bone marrow suppression. Therefore, we expect that the combination of MPBX with IDA will be useful for leukemia chemotherapy.
Sadzuka
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan. sadzuka@u-shizuoka-ken.ac.jp.
Egawa
Y
Y
Sugiyama
T
T
Sawanishi
H
H
Miyamoto
K
K
Sonobe
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D015255:Idarubicin / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014970:Xanthines / Q000494:pharmacology*
C111594:1-methyl-3-propyl-7-butylxanthine; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D014970:Xanthines; D015255:Idarubicin