Potent anticancer activity of pyrrolidine dithiocarbamate-copper complex against cisplatin-resistant neuroblastoma cells.
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.
Zhang
Haiyuan
H
aCarman & Ann Adams Department of Pediatrics bDepartment of Radiology cBarbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan, USA.
Wu
Jiu-sheng
JS
Peng
Fangyu
F
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D020128:Inhibitory Concentration 50; D008858:Microscopy, Phase-Contrast; D015394:Molecular Structure; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D003603:Cytotoxins; D011759:Pyrrolidines; D013859:Thiocarbamates; D016159:Tumor Suppressor Protein p53; C020972:pyrrolidine dithiocarbamic acid; D003300:Copper; D004247:DNA; D002945:Cisplatin