Systematic analysis of the antiproliferative effects of novel and standard anticancer agents in rhabdoid tumor cell lines

Abstract

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.