Abstract:
There is considerable interest among basic and clinical researchers in novel drugs with activity
against leukemia. The vast history of experience of traditional Chinese medicine (TCM) with medicinal plants may
facilitate the identification of novel antileukemic compounds. In the present investigation, we tested 22 drugs for
their activity toward CCRF-CEM cell lines: artesunate, artemisinin, baicalein, baicalin, berberine, bufalin,
cantharidin, cephalotaxine, curcumin, daidzein, daidzin, diallyl disulfide, ginsenoside Rh2, glycyrrhizic acid,
isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin, quercetin, tannic acid, and tetrahydronardosinon.
As compounds from folk medicinal remedies are sometimes looked upon as alternative medicine with
orne hesitation or criticism, we investigated only chemically pure compounds and tested the drugs independently
two different laboratories in Germany and Australia. We used CCRF-CEM parental cells and doxorubicin selected
P-glycoprotein (P-gp)/MDRl-expressing CEM/ADR5000, vinblastine-selected P-gpIMDRl-expressing
CEMNLB100, and epirubicin-selected multidrug resistance-related protein 1 (MRPl)-expressing CEM/E1000
sublines thereof. While CEM/ADR5000, CEMNLB100, and CEM/E1000 cells were highly resistant to the
corresponding selecting agents, no or only minimal degrees of cross-resistance were observed to TCM drugs in
both growth inhibition assay and MTT assay (range from 0.4- to 8-fold). Homoharringtonine, artesunate, and
bufalin were most active among this panel of compounds. As shown by flow cytometry, artesunate significantly
increased daunorubicin accumulation in CEM/El000 cells, but not in CEM/VLB100 or CCRF-CEM parental cells.
Bufalin caused a small, but significant increase in daunorubicin accumulation in CEMNLB100 and CEM/E1000cells. As artesunate and bufalin showed both antileukemic activity if applied alone and modulation activity in
combination with daunorubicin in multidrug-resistant (MDR) cells, these two drugs may be suitable for novel
combination treatment regimens to improve leukemia cell killing.
