Rhabdoid tumors are highly aggressive pediatric
malignancies. Although the prognosis of children with
rhabdoid tumors has improved, it still remains dismal and long-term survivors suffer from severe side effects of current therapeutic approaches. The objective of our study was to explore the toxicity of standard and novel anticancer drugs against
rhabdoid tumors in vitro and to prioritize them for future preclinical and clinical studies. Antitumor activity of 10 standard anticancer drugs (
doxorubicin,
idarubicin,
mitoxantrone,
actinomycin D,
temozolomide,
carmustine,
oxaliplatin,
vinorelbine,
methotrexate,
thiotepa), five target-specific drugs (
sorafenib,
imatinib,
roscovitine,
rapamycin,
ciglitazone) and two herbal compounds (
curcumin and
apigenin) was assessed by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium
bromide (MTT) cell proliferation assay on three
rhabdoid tumor cell lines, A204, G401, and BT16, derived from different anatomical sites. Comparable with their high clinical activity,
anthracyclines inhibited
tumor cell proliferation by 50% (GI50) in the nanomolar range.
Actinomycin D exhibited the lowest GI50 values overall ranging from 2.8x10(-6) nmol/l for G401 to 3.8 nmol/l for A204 cells while
thiotepa was the only alkylating
drug that inhibited
tumor cell growth in clinically relevant concentrations. Target-specific drugs, such as
sorafenib,
roscovitine, and
rapamycin, showed promising results as well. In this report, we show for the first time that
apigenin and
curcumin effectively inhibit
rhabdoid tumor cell growth. Supporting earlier reports we conclude that
cyclin D1 seems to be an excellent target in the treatment of
rhabdoid tumors.
Idarubicin or
mitoxantrone represent potent alternatives to
doxorubicin, and
vinorelbine may substitute
vincristine in future clinical trials.