NDLI: Cell cycle arrest in cultured neuroblastoma cells exposed to a bis(thiosemicarbazonato) metal complex

Content Provider	Springer Nature Link
Author	Bica, Laura Meyerowitz, Jodi Parker, Sarah J. Caragounis, Aphrodite Du, Tai Paterson, Brett M. Barnham, Kevin J. Crouch, Peter J. White, Anthony R. Donnelly, Paul S.
Copyright Year	2010
Abstract	Brain tumors such as neuroblastomas and gliomas are often refractory to current treatments. Development of metal-based drugs may offer an alternative approach due to the ability to deliver radionuclides or cytotoxic metals to the tumor. Previous studies have shown that diacetyl-bis(N(4)-methylthiosemicarbazonato)-copper(II) (CuII(atsm)) can selectively target hypoxic tumors and this feature has been utilized for development of imaging and radiotherapy. However, we have recently shown that glyoxal-bis(N(4)-methylthiosemicarbazonato)-copper(II) (CuII(gtsm)) can target the brain in animal models of neurodegeneration. Unlike CuII(atsm), CuII(gtsm) is able to release Cu intracellularly under normoxic conditions. Glyoxal-bis(thiosemicarbazones) have reported anticancer effects but little is known about the cellular mechanisms involved. Therefore, in this study, we used protein microarray analysis to investigate the effect of CuII(gtsm) on neuroblastoma cell growth in vitro. Treatment of the human neuroblastoma cell line BE(2)-M17, resulted in cell cycle arrest as assessed by fluorescent activated cell sorting (FACS) analysis. Rapidly arrested growth was not associated with onset of apoptosis. Instead, protein microarray analysis revealed that CuII(gtsm) rapidly and potently reduced cyclin D1 expression, while increasing Kip2 expression. Other changes observed were decreased Cdk7 expression and activation of CHK2. These changes may be associated with the cell cycle arrest. We also observed a potent decrease of total and phosphorylated insulin-like growth factor receptor (IGF-IR) by CuII(gtsm) which is associated with modulation of cyclin D1 expression. Our studies reveal important insights into the potential anticancer activity of CuII(gtsm). Further studies are needed to examine the therapeutic potential of CuII(gtsm) and other bis(thiosemicarbazonato) metal complexes as metallo-drugs for treatment of systemic or brain tumors.
Starting Page	117
Ending Page	133
Page Count	17
File Format	PDF
ISSN	09660844
Journal	BioMetals
Volume Number	24
Issue Number	1
e-ISSN	15728773
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-10-08
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Copper Cell cycle Bis(thiosemicarbazone) Protein microarray Physical Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences

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