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Anticancer Drugs. 2008 Feb;19(2):125-32. doi: 10.1097/CAD.0b013e3282f2bdff.

Potent anticancer activity of pyrrolidine dithiocarbamate-copper complex against cisplatin-resistant neuroblastoma cells.

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aCarman & Ann Adams Department of Pediatrics bDepartment of Radiology cBarbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan, USA.


Effective drugs are urgently needed for the treatment of advanced neuroblastoma refractory to conventional chemotherapy. Pyrrolidine dithiocarbamate (PDTC) is a copper-binding ligand, which showed cytotoxicity on many human tumor cells after binding with copper ions. In this study, we synthesized a copper-PDTC complex, which was characterized as a Cu(PDTC)2 complex, with elemental analyses (Fourier transform infrared, electrospray ionization mass spectra, and ultraviolet-visible spectroscopy). The Cu(PDTC)2 complex suppressed the proliferation of BE(2)C cells, a human neuroblastoma cell line, with an IC50 of 8.0 micromol/l, which was more potent than cisplatin (IC50 of 80 micromol/l). Treatment of BE(2)C cells with the Cu(PDTC)2 complex caused the S-phase arrest of cell cycle progression, cellular apoptosis, and necrosis, and increased the expression of p53 protein. The Cu(PDTC)2 complex holds potential as a new drug for the treatment of refractory neuroblastoma in children.

[Indexed for MEDLINE]

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