Evaluation of the in vitro antiproliferative properties of four novel anthracyclines YM1, 3, 4 and 6 in human leukemia cell lines.
The antitumor activity of novel doxorubicin analogues YM1, YM3, YM4 and YM6 was evaluated against drug sensitive U937 monocytic leukemia and CCRF-CEM lymphoid leukemia cell lines, as well as drug resistant CEM/VLB100 lymphoid multidrug resistant leukemia cell line by a [3H]thymidine incorporation assay. Different antileukemic activities of these new anthracyclines were observed in our studies. These novel anthracyclines produced a dose- and time-dependent inhibition in all the leukemic cell lines tested, while YM1 and YM3 were more effective than YM4 and YM6 against all the leukemic cell lines. The antitumor activity of all these novel analogues was lower than that of doxorubicin or epidoxorubicin in drug sensitive leukemic cells. The relative resistance values (IC50 of resistant cell line/IC50 of sensitive parental cell line) of YM1, 3, 4 and 6 were 27, 7, 5 and 14 respectively. These were lower than the resistance values for ADM and EDR which were 45 and 40 respectively. YM3 had a similar antileukemic activity against the CEM/VLB100 drug resistant leukemic cell line to ADM or EDR with a lower relative resistance value and a slightly increased IC50 value. Our results suggest that YM3 may be used in high dose for the clinical treatment of leukemias with possible less cardiotoxicity as well as less drug resistance.
Jiang
X R
XR
Department of Hematology, Royal London Hospital, U.K.
Newland
A C
AC
Macey
M G
MG
Jenkins
G C
GC
Miki
T
T
Adachi
K
K
Yamabe
S
S
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D015251:Epirubicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; C079109:N-(3-pyridylmethyl)adriamycin; C079111:N-(3-pyridylmethyl)dihydroepidoxorubicin; C079112:N,N-bis(3-pyridylmethyl)adriamycin; C079110:N-(3-pyridylmethyl)epidoxorubicin; D015251:Epirubicin; D004317:Doxorubicin